Compositions and methods for promoting payload delivery in cells

Abstract

Disclosed herein, in some aspects, are compositions of lipid delivery particles used to deliver a payload to a target cell and methods of producing the like. Lipid delivery particles can comprise ectosomes, exosomes, nanoparticles, or other classes of extracellular vesicles suitable for transporting a payload. Lipid delivery particles can comprise a plasma membrane recruitment element comprising a mutant gag polyprotein.

Description

COMPOSITIONS AND METHODS FOR PROMOTING PAYLOAD DELIVERY IN CELLSCROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 506,783, filed June 7, 2023; which is incorporated herein by reference in their entirety.BACKGROUND

[0002] Delivery of therapeutic payloads into the cells has been a significant challenge in drug development because payloads, such as proteins, cannot freely diffuse across the cell membrane. Although viral based constructs have been developed to deliver therapeutic payloads, these constructs often have low efficacy and / or create considerable side effects. There is a need for improved delivery of payloads into cells.SUMMARY

[0003] In some aspects, disclosed herein is a lipid delivery particle comprising (a) a lipid membrane; (b) a plasma membrane recruitment element comprising a mutant gag polyprotein, and (c) a payload encapsulated by the lipid containing membrane, and wherein the plasma membrane recruitment element lacks at least a fragment of a matrix protein, at least a fragment of a RNA-binding phosphoprotein, at least a fragment of a capsid protein, a gag -endogenous protease cleavage sequence, or at least a fragment of a nucleocapsid protein; and wherein (1) the plasma membrane recruitment element comprises (i) a full- length capsid protein; (ii) a full-length matrix protein; (iii) a heterologous sequence; (iv) at least a portion of a nucleocapsid protein; (v) two or more particle budding motifs; (vi) at least a portion of a P6 domain; or (vii) two spacer peptides; (2) the lipid delivery particle further comprises an envelope protein, wherein the envelope protein comprises an envelope protein from human endogenous retrovirus (HERV) or a mutant thereof; or (3) the plasma membrane recruitment element is fused to (i) a cleavable linker; (ii) a membrane penetrating peptide; or (iii) a post-translational modification motif. In some cases, the mutant gag polyprotein is a mutant of a wild-type gag polyprotein of a retrovirus. In some cases, the retrovirus is oncoretroviruses, lentiviruses, or spumaviruses. In some cases, the retrovirus is Human Immunodeficiency Virus (HIV), Moloney Murine Leukemia Virus (MMLV), or Rous sarcoma virus (RSV). In some cases, the mutant gag polyprotein is a mutant of a wild-type gag polyprotein of a human endogenous retrovirus (HERV) or a gag homology protein (optionally human Arc). In some cases, the HERV is HERV-K or HERV-W. In some cases, the HERV-K is HERV-K113, HERV-K101, HERV- K102, HERV-K104, HERV-K107, HERV-K108, HERV-K109, HERV-K115, HERV-K1 lp22, or HERV-K12ql3. In some cases, the mutant gag polyprotein is a mutant of a wild-type gag polyprotein of a HERV-K 113. In some cases, the mutant gag polyprotein is a mutant of a wild type gag polyprotein of an alpharetrovirus, a betaretrovirus, or a deltaretrovirus, optionally the wild type gag polyprotein comprises the sequence set forth in any one of SEQ ID NOs: 285-298. In some cases, the lipid delivery particle comprises a chimeric protein comprising the plasma membrane recruitment element and the payload. In some cases, the at least a fragment of the matrix protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%,99% or 100% of the entire amino acid sequence of the matrix protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the matrix protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the matrix protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the RNA-binding phosphoprotein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the RNA-binding phosphoprotein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the RNA-binding phosphoprotein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the RNA-binding phosphoprotein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the capsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the capsid protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the capsid protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the capsid protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the nucleocapsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the nucleocapsid protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the nucleocapsid protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the nucleocapsid protein of a corresponding wild type gag polyprotein. In some cases, the at least a portion of the P6 domain comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the P6 domain of the corresponding wild type gag polyprotein. In some cases, the at least a portion of the P6 domain comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the P6 domain of a corresponding wild type gag polyprotein. In some cases, the plasma membrane recruitment element comprises the full- length capsid protein. In some cases, the plasma membrane recruitment element comprises the full-length matrix protein. In some cases, the plasma membrane recruitment element comprises the heterologous sequence. In some cases, the heterologous sequence is fused to a fragment of the capsid protein, a matrix protein or a fragment thereof, a nucleocapsid protein or a fragment thereof, a particle budding motif or a fragment thereof. In some cases, the plasma membrane recruitment element lacks the matrix protein. In some cases, the fragment of the capsid protein is a C-terminal fragment comprising a major homology region (MHR). In some cases, the heterologous sequence is fused to the N-terminal of the fragment of thecapsid protein or a particle budding motif (optionally a late domain of RSV). In some cases, the heterologous sequence is a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof. In some cases, the plasma membrane recruitment element comprises at least a portion of the nucleocapsid protein; optionally a N-terminal fragment of the nucleocapsid protein; optionally a C- terminal fragment of the nucleocapsid protein). In some cases, the plasma membrane recruitment element comprises two or more particle budding motifs. In some cases, (a) at least one of the two or more particle budding motifs is endogenous, (b) at least one of the two or more particle budding motifs is heterologous (optionally RSV P2B or a mutant thereof), (c) at least one of the two or more particle budding motifs comprises a PTAP motif, a PPPY motif, a PPXY motif, a YXXL motif, a YPXnL motif, or any combinations thereof, wherein n is an integer from 1 to 5; or (d) at least one of the two or more particle budding motifs comprises a sequence listed in Table 5. In some cases, the plasma membrane recruitment element comprises at least a portion of the P6 domain. In some cases, the plasma membrane recruitment element comprises at least a N-terminal fragment of the P6 domain or at least a C-terminal fragment of the P6 domain. In some cases, the plasma membrane recruitment element comprises the mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of HIV. In some cases, the plasma membrane recruitment element is fused to the post-translational modification motif is selected from the group consisting of: a myristoylation motif, an acetylation motif, an isoprenylation motif, a palmitoylation motif, a famesylation motif, and any combinations thereof. In some cases, the plasma membrane recruitment element comprises the two spacer peptides. In some cases, at least one of the two spacer peptides is P2 domain or Pl domain. In some cases, the two spacer peptides are P2 domain and Pl domain. In some cases, the plasma membrane recruitment element comprises the mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of HIV. In some cases, the lipid delivery particle further comprises the envelope protein, and wherein the envelope protein comprises the envelope protein from human endogenous retrovirus (HERV) or a mutant thereof. In some cases, the envelope protein comprises hENVHl, hENVH2, hENVH3, hENVKl, hENVK2, hENVK3, hENVK4, hENVK5, hENVK6, hENVT, hENVW, hENVFRD, hENVR, hENVR(b), hENVR(c)2, hENVR(c) 1, or hENVKcon, or a mutant thereof. In some cases, the plasma membrane recruitment element is fused to the cleavable linker, and wherein the cleavable linker connects the plasma membrane recruitment element and the payload. In some cases, the plasma membrane recruitment element is fused to the membrane penetrating peptide. In some cases, (a) the membrane penetrating peptide is linked to the payload or the plasma membrane recruitment element; or (b) the membrane penetrating peptide is linked between the payload and the plasma membrane recruitment element. In some cases, the membrane penetrating peptide comprises a sequence having at least about 80% sequence identity to a sequence listed in Table 6.

[0004] In some cases, the mutant gag polyprotein is a mutant of a wild-type gag polyprotein of HIV, and wherein (1) the plasma membrane recruitment element is fused to the cleavable linker, the membrane penetrating peptide, or the post-translational modification motif; or (2) wherein the lipid delivery particle further comprises the envelope protein, and wherein the envelope protein comprises the envelope protein from human endogenous retrovirus (HERV) or a mutant thereof. In some cases, the plasma membranerecruitment element comprises (a) at least a fragment of matrix protein of an HIV gag, optionally a N- terminal fragment of the matrix protein of the HIV gag; or (b) a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof. In some cases, wherein the plasma membrane recruitment element comprises at least a fragment of capsid protein of the HIV gag; optionally wherein the plasma membrane recruitment element comprises a full-length capsid protein of the HIV gag; optionally wherein the plasma membrane recruitment element comprises a C-terminal fragment of capsid protein of the HIV gag. In some cases, wherein the plasma membrane recruitment element comprises a spacer peptide of the HIV gag; optionally wherein the plasma membrane recruitment element comprises a P2 domain of the HIV gag, a Pl domain of the HIV gag, or both. In some cases, the plasma membrane recruitment element comprises (a) a heterologous domain, optionally wherein the heterologous domain comprises a multimerization motif, optionally wherein the multimerization motif forms parallel homodimers or parallel heterodimers (optional DZF), optionally wherein the parallel homodimers comprise a coiled-coil, optionally wherein the coiled-coil is a leucine zipper, optionally wherein the plasma membrane recruitment element lacks nucleocapsid protein of the HIV gag; or (b) a full-length nucleocapsid protein of the HIV gag or a fragment thereof. In some cases, the plasma membrane recruitment element comprises a particle budding motif; optionally wherein the plasma membrane recruitment element comprises two or more particle budding motifs; optionally wherein at least one of the particle budding motifs is (a) a particle budding motif of the HIV gag (optionally a N-terminal fragment of the P6 domain of the HIV gag, a PTAP motif, or a full-length P6 domain of the HIV gag); or (b) a heterologous particle budding motif (optionally RSV P2B or a mutant thereof or a sequence listed in Table 5). In some cases, the plasma membrane recruitment element lacks a matrix protein of the HIV gag, and wherein the plasma membrane recruitment element comprises a N-terminal myristoylation motif, the full-length capsid protein of the HIV gag or a fragment thereof, the multimerization motif (optionally a DZF), and a heterologous particle budding motif (optionally a late domain of RSV) arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element lacks a matrix protein of the HIV gag, and wherein the plasma membrane recruitment element comprises a heterologous particle budding motif (optionally a late domain of RSV), a N-terminal myristoylation motif, the full-length capsid protein of the HIV gag or a fragment thereof, the multimerization motif (optionally a DZF), arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises (a) the N-terminal fragment of the matrix protein of the HIV gag or the pleckstrin homology (PH) domain or a mutant thereof; (b) the full-length capsid protein of the HIV gag or a fragment thereof; (c) the multimerization motif (optionally a leucine zipper) or the full-length nucleocapsid protein of the HIV gag or a fragment thereof; and (d) the particle budding motif; optionally wherein the (a)-(d) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the plasma membrane recruitment element further comprises the P2 domain of the HIV gag located at a position between (b) and (c). In some cases,the plasma membrane recruitment element comprises: (a) the particle budding motif; (b) the N-terminal fragment of the matrix protein of the HIV gag or the pleckstrin homology (PH) domain or a mutant thereof; (c) the full-length capsid protein of the HIV gag or a fragment thereof; and (d) the multimerization motif (optionally a leucine zipper) or the full-length nucleocapsid protein of the HIV gag or a fragment thereof; and; optionally wherein the (a)-(d) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the plasma membrane recruitment element further comprises the P2 domain of the HIV gag located at a position between (c) and (d). In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag or a fragment thereof, the P2 domain of the HIV gag, the full-length capsid protein of the HIV gag, the Pl domain of the HIV gag, and the P6 domain of the HIV gag or a fragment thereof, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag or a fragment thereof, the P2 domain of the HIV gag, the leucine zipper, and the P6 domain of the HIV gag or a fragment thereof, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag or a fragment thereof, the P2 domain of the HIV gag, the leucine zipper, and a particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises a particle budding motif, the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag or a fragment thereof, the P2 domain of the HIV gag, and the leucine zipper, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif, a C-terminal fragment of the HIV gag, the P2 domain of the HIV gag, the leucine zipper, and a second particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, optionally a first particle budding motif, the full-length capsid protein of the HIV gag or a fragment thereof, optionally the P2 domain of the HIV gag, the leucine zipper, and optionally a second particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the first and the second particle budding motif; optionally wherein each of the first and the second particle budding motifs independently (a) is the particle budding motif of the HIV gag; (b) is a heterologous particle budding motif (optionally RSV P2B or a mutant thereof); or (c) comprises a sequence listed in Table 5. In some cases, the plasma membranerecruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the heterologous particle budding motif, the full-length capsid protein of the HIV gag, the P2 domain, the leucine zipper, and the particle budding motif of the HIV gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof. In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag or the pleckstrin homology (PH) domain or a mutant thereof, the full-length capsid protein of the HIV gag, the P2 domain, the full-length nucleocapsid protein of the HIV gag, and the particle budding motif of the HIV gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof.

[0005] In some aspects, disclosed herein is a lipid delivery particle comprising (a) a lipid membrane; (b) a plasma membrane recruitment element comprising a mutant gag polyprotein that is not from HIV, and (c) a payload encapsulated by the lipid containing membrane, wherein the plasma membrane recruitment element lacks at least a fragment of a matrix protein, at least a fragment of a RNA-binding phosphoprotein, at least a fragment of a capsid protein, a gag-endogenous protease cleavage sequence, or at least a fragment of a nucleocapsid protein. In some cases, the mutant gag polyprotein is mutant of a wild-type gag polypeptide of a retrovirus; optionally wherein the retrovirus is oncoretroviruses, lentiviruses, or spumaviruses; optionally wherein the retrovirus is MMLV. In some cases, the mutant gag polyprotein is mutant of a wild-type gag polypeptide of a human endogenous retrovirus (HERV) or a gag homology protein (optionally human Arc or PEG10); optionally wherein the HERV is HERV-K or HERV-W; optionally wherein the HERV-K is HERV-K 113, HERV-K101, HERV-K 102, HERV-K 104, HERV-K107, HERV-K108, HERV-K109, HERV-K115, HERV-Kl lp22, or HERV-K 12ql3; optionally wherein the mutant gag polyprotein is mutant of a wild-type gag polypeptide of HERV-K 113 or a hGAGKcon. In some cases, the mutant gag polyprotein is a mutant of a wild type gag polyprotein of an alpharetrovirus, a betaretrovirus, or a deltaretrovirus, optionally the wild type gag polyprotein comprises the sequence set forth in any one of SEQ ID NOs: 285-298. In some cases, the lipid delivery particle comprises a chimeric protein comprising the plasma membrane recruitment element and the payload. In some cases, the at least a fragment of the matrix protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the matrix protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the matrix protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the matrix protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the RNA-binding phosphoprotein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the RNA-binding phosphoprotein of a corresponding wild type gag polyprotein. In some cases, the atleast a fragment of the RNA-binding phosphoprotein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the RNA-binding phosphoprotein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the capsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the capsid protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the capsid protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the capsid protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the nucleocapsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the nucleocapsid protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the nucleocapsid protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the nucleocapsid protein of a corresponding wild type gag polyprotein. In some cases, the plasma membrane recruitment element lacks the at least a fragment of a matrix protein; optionally wherein the plasma membrane recruitment element lacks a N-terminal fragment of the matrix protein. In some cases, the plasma membrane recruitment element lacks the at least a fragment of a RNA-binding phosphoprotein; optionally wherein the plasma membrane recruitment element comprises a mutant of a wild-type gag polyprotein of MMLV. In some cases, the plasma membrane recruitment element lacks the at least a fragment of a capsid protein; optionally wherein the plasma membrane recruitment element lacks a N-terminal fragment of the capsid protein, a C-terminal fragment of the capsid protein, or both. In some cases, the plasma membrane recruitment element lacks the gag -endogenous protease cleavage sequence. In some cases, the plasma membrane recruitment element lacks the at least a fragment of a nucleocapsid protein; optionally wherein the plasma membrane recruitment element lacks a N-terminal fragment of the nucleocapsid protein, a C-terminal fragment of the nucleocapsid protein, or both; optionally wherein the plasma membrane recruitment element lacks the nucleocapsid protein. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of MMLV. In some cases, the plasma membrane recruitment element comprises (a) a matrix protein of the MMLV gag (optionally full-length matrix protein of the MMLV gag, a N-terminal fragment or a C-terminal fragment of the full-length matrix protein of the MMLV gag), a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof; (b) a capsid protein of the MMLV gag or a mutant thereof, optionally wherein the capsid protein of the MMLV gag or a mutant thereof is a full-length capsid protein of the MMLV gag, or a N-terminal fragment of or a C-terminal fragment of the full-length capsid protein of the MMLV gag; (c) heterologous domain, optionally wherein the heterologous domain comprises a multimerization motif (optionally a leucine zipper); and (d) an optional particle budding motif, optionally wherein the particlebudding motif is particle budding motif of the MMLV gag; optionally wherein the particle budding motif is a heterologous particle budding motif; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof or a sequence listed in Table 5; optionally wherein the (a)-(d) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the plasma membrane recruitment element further comprises a P12 domain of the MMLV gag or a mutant thereof located between (a) and (b), optionally wherein the P12 domain of the MMLV gag or a mutant thereof is a full-length P12 domain of the MMLV gag, a N-terminal fragment of the full-length P12 domain of the MMLV gag, a C-terminal fragment of the full-length P12 domain of the MMLV gag, or a fragment of the full-length P12 domain of the MMLV gag fused to a heterologous particle budding motif (optionally RSV P2B or a mutant thereof or a sequence listed in Table 5). In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the full-length matrix protein of the MMLV gag, the full-length P12 domain of the MMLV gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the MMLV gag or a fragment thereof, and the leucine zipper, arranged in order from a N- terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length P12 domain of the MMLV gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the MMLV gag or a fragment thereof, the leucine zipper, and optionally the particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the particle budding motif, the pleckstrin homology (PH) domain or a mutant thereof, the full-length P12 domain of the MMLV gag or a fragment there of that is fused to a heterologous particle budding motif, the full- length capsid protein of the MMLV gag or a fragment thereof, and the leucine zipper, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the full-length matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag or a fragment thereof, the leucine zipper, and the particle budding motif, arranged in order from a N- terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the particle budding motif, the N-terminal fragment of the full-length matrix protein of the MMLV gag, the full- length capsid protein of the MMLV gag or a fragment thereof, and the leucine zipper, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length capsid protein of the MMLV gag or a fragment thereof, the leucine zipper, and the particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the particle budding motif,the pleckstrin homology (PH) domain or a mutant thereof, the full-length capsid protein of the MMLV gag or a fragment thereof, and the leucine zipper, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of hGAGKcon; optionally wherein the plasma membrane recruitment element comprises a N-terminal myristoylation motif of the hGAGKcon gag, a full-length capsid protein of the hGAGKcon gag or a fragment thereof, a multimerization motif (optionally a DZF), and a particle budding motif (optionally a late domain of RSV); optionally wherein the plasma membrane recruitment element comprises a N-terminal myristoylation motif of an HIV gag, a full-length capsid protein of the hGAGKcon gag or a fragment thereof, a multimerization motif (optionally a DZF), and a particle budding motif (optionally a late domain of RSV). In some cases, the plasma membrane recruitment element comprises a mutant gag polyp rotein that is a mutant of a wild-type gag polyprotein of HERV-K113. In some cases, the plasma membrane recruitment element comprises: (a) a matrix protein of the HERV- K113 gag (optionally full-length matrix protein of the HERV-K113 gag, a N-terminal fragment or a C- terminal fragment of the full-length matrix protein of the HERV-K113 gag), a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof; (b) a capsid protein of the HERV-K113 gag or a mutant thereof, optionally wherein the capsid protein of the HERV-K113 gag or a mutant thereof is a full-length capsid protein of the HERV-K113 gag, or a N-terminal fragment of or a C-terminal fragment of the full-length capsid protein of the HERV-K113 gag; (c) heterologous domain, optionally wherein the heterologous domain comprises a multimerization motif (optionally a leucine zipper); and (d) an optional particle budding motif, optionally wherein the particle budding motif is particle budding motif of the HERV-K113 gag; optionally wherein the particle budding motif is a heterologous particle budding motif; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof or a sequence listed in Table 5); (e) an optional QP1 domain of the HERV-K113 gag; and (f) an optional QP2 domain of the HERV-K113 gag; optionally wherein (a)-(f) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the plasma membrane recruitment element further comprises a Pl 5 domain of the HERV-K113 gag or a mutant thereof, optionally wherein the P15 domain of the HERV-K113 gag or a mutant thereof is a full-length P15 domain of the HERV-K113 gag, a N-terminal fragment of the full-length P15 domain of the HERV-K113 gag, a C-terminal fragment of the full-length P15 domain of the HERV-K113 gag, or a fragment of the full-length P15 domain of the HERV-K113 gag fused to a heterologous particle budding motif (optionally RSV P2B or a mutant thereof or a sequence listed in Table 5). In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the full-length matrix protein of the HERV-K113 gag, the full-length P15 domain of the HERV-K113 gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, the optional QP1 domain of the HERV-K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, theplasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length P15 domain of the HERV-K113 gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, optionally the particle budding motif, the optional QP1 domain of the HERV- K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the full- length matrix protein of the HERV-K113 gag, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, the particle budding motif, the optional QP1 domain of the HERV- K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, the particle budding motif, the optional QP1 domain of the HERV-K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the QP 1 domain and the QP2 domain of the HERV-K113 gag. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of RSV; optionally wherein the plasma membrane recruitment element comprises a matrix protein of the RSV gag and a late domain of the RSV gag; optionally wherein the plasma membrane recruitment element comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a full-length nucleocapsid protein of the RSV; optionally wherein the plasma membrane recruitment element comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a fragment of the nucleocapsid protein of the RSV; optionally wherein the plasma membrane recruitment element further comprises a N-terminal myristoylation motif. In some cases, the plasma membrane recruitment element comprises one, two, or three particle budding motif, wherein each of the particle budding motif is selected from a sequence listed in Table 5. In some cases, the plasma membrane recruitment element comprises a major homology region (MHR). In some cases, the plasma membrane recruitment element comprises the heterologous sequence; optionally wherein the heterologous sequence is fused to a fragment of the matrix protein, optionally the N-terminal of the fragment of the matrix protein; optionally wherein the heterologous sequence is a pleckstrin homology (PH) domain or a mutant thereof; optionally wherein the PH domain is a human PH domain; optionally wherein the fragment of the matrix protein lacks a N-terminal myristoylation motif, a N-terminal glycine, a highly basic region (HBR), a N-terminal fragment, or any combination thereof. In some cases, the chimeric protein comprises a cleavable linker; optionally wherein the cleavable linker connects the plasma membrane recruitment element and the payload. In some cases, the chimeric protein comprises a nuclear localization signal (NLS) sequence. In some cases, the chimeric protein comprises a nuclear export signal (NES) sequence. In some cases, the chimeric protein comprises the membrane penetratingpeptide, optionally wherein (a) the membrane penetrating peptide is linked to the payload or the plasma membrane recruitment element; or (b) the membrane penetrating peptide connects the payload and the plasma membrane recruitment element; optionally wherein the membrane penetrating peptide comprises a sequence having at least about 80% sequence identity to a sequence listed in Table 6. In some cases, the chimeric protein comprises the post-translational modification motif that is fused directly to (a) the payload; or (b) the plasma membrane recruitment element; optionally wherein the post-translational modification motif comprises a myristoylation motif, an acetylation motif, an isoprenylation motif, a palmitoylation motif, a famesylation motif, or combinations thereof. In some cases, the chimeric protein comprises the plasma membrane recruitment element, an optional NLS, the cleavable linker, and the payload arranged in order from N-terminus of the chimeric protein to C-terminus of the chimeric protein. In some cases, the lipid delivery particle comprises the envelope protein; optionally wherein the envelope protein is a retroviral envelope protein or a mutant thereof; optionally wherein the envelope protein is an envelope protein from human endogenous retrovirus (HERV) or a mutant thereof. In some cases, the plasma membrane recruitment element forms part of a basic structure of the lipid delivery particle (optionally a protein core). In some cases, the payload comprises an antibody, a cytokine, a therapeutic protein, a small molecule therapeutics, a therapeutic DNA, and a therapeutic RNA, a ribonucleoprotein, a zinc-finger, a transcription activator-like effector (TALE), or a CRISPR-based genome editor, or any combinations thereof; optionally wherein the payload comprises a NLS, optionally wherein the NLS is an endogenous NLS or a heterologous NLS. In some cases, the lipid delivery particle further comprises a second plasma membrane recruitment element; optionally wherein the second plasma membrane recruitment element is the same as the plasma membrane recruitment element; optionally wherein the second plasma membrane recruitment element is a retroviral gag or a mutant thereof, a HERV gag or a mutant thereof, a pleckstrin homology (PH) domain or a mutant thereof, or a membrane protein or a transmembrane domain thereof or a mutant thereof. In some cases, the second plasma membrane recruitment element forms part of a basic structure of the lipid delivery particle (optionally a protein core). In some cases, the lipid delivery particle further comprises a protease; optionally wherein the protease is a retroviral protease. In some cases, the plasma membrane recruitment element is linked to the protease, optionally via a cleavable linker. In some cases, the second plasma membrane recruitment element is linked to the protease, optionally via a cleavable linker. In some cases, the plasma membrane recruitment element further comprises one or more mutant gag -endogenous protease cleavage sequences relative to a corresponding wildtype gag-endogenous protease cleavage sequence, and wherein the one or more mutant gag-endogenous protease cleavage sequences have higher cleavage efficiency than that of the corresponding wildtype gag -endogenous protease cleavage sequence.

[0006] In some aspects, disclosed herein is a recombinant protein comprising a plasma membrane recruitment element comprising a mutant gag polyprotein, wherein the plasma membrane recruitment element lacks at least a fragment of a matrix protein, at least a fragment of a RNA-binding phosphoprotein, at least a fragment of a capsid protein, a gag-endogenous protease cleavage sequence, or at least a fragment of a nucleocapsid protein; and wherein (1) the plasma membrane recruitment elementcomprises (i) a full-length capsid protein; (ii) a full-length matrix protein; (iii) a heterologous sequence; (iv) at least a portion of a nucleocapsid protein; (v) two or more particle budding motifs; (vi) at least a portion of a P6 domain; or (vii) two spacer peptides; or (2) the plasma membrane recruitment element is fused to (i) a cleavable linker; (ii) a membrane penetrating peptide; or (iii) a post-translational modification motif. In some cases, the mutant gag polyprotein is a mutant of a wild-type gag polyprotein of a retrovirus; optionally wherein the retrovirus is oncoretroviruses, lentiviruses, or spumaviruses; optionally wherein the retrovirus is Human Immunodeficiency Virus (HIV), Moloney Murine Leukemia Virus (MMMLV), or Rous sarcoma virus (RSV). In some cases, the mutant gag polyprotein is a mutant of a wild-type gag polyprotein of a human endogenous retrovirus (HERV); optionally wherein the HERV is HERV-K or HERV-W; optionally wherein the HERV-K is HERV-K113, HERV-K101, HERV-K102, HERV-K104, HERV-K107, HERV-K108, HERV-K109, HERV-K115, HERV-Kl lp22, or HERV- K12ql3; optionally wherein the mutant gag polyprotein is a mutant of a wild-type gag polyprotein of a HERV-K 113. In some cases, the mutant gag polyprotein is a mutant of a wild type gag polyprotein of an alpharetrovirus, a betaretrovirus, or a deltaretrovirus, optionally the wild type gag polyprotein comprises the sequence set forth in any one of SEQ ID NOs: 285-298. In some cases, the at least a fragment of the matrix protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the matrix protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the matrix protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the matrix protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the RNA-binding phosphoprotein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the RNA-binding phosphoprotein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the RNA-binding phosphoprotein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the RNA- binding phosphoprotein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the capsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the capsid protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the capsid protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the capsid protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the nucleocapsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the nucleocapsid protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the nucleocapsidprotein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the nucleocapsid protein of a corresponding wild type gag polyprotein. In some cases, the at least a portion of the P6 domain comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the P6 domain of the corresponding wild type gag polyprotein. In some cases, the at least a portion of the P6 domain comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the P6 domain of a corresponding wild type gag polyprotein. In some cases, the plasma membrane recruitment element comprises the full-length capsid protein. In some cases, the plasma membrane recruitment element comprises the full-length matrix protein. In some cases, the plasma membrane recruitment element comprises the heterologous sequence; optionally wherein the heterologous sequence is fused to a fragment of the capsid protein, a matrix protein or a fragment thereof, a nucleocapsid protein or a fragment thereof, a particle budding motif or a fragment thereof; optionally wherein the plasma membrane recruitment element lacks the matrix protein; optionally wherein the fragment of the capsid protein is a C-terminal fragment. In some cases, the heterologous sequence is fused to the N-terminal of the fragment of the capsid protein or a particle budding motif (optionally a late domain of RSV); optionally wherein the heterologous sequence is a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof. In some cases, the plasma membrane recruitment element comprises at least a portion of a nucleocapsid protein; optionally a N-terminal fragment of the nucleocapsid protein; optionally a C-terminal fragment of the nucleocapsid protein). In some cases, the plasma membrane recruitment element comprises two or more particle budding motifs; optionally wherein (a) at least one of the two or more particle budding motifs is endogenous, (b) at least one of the two or more particle budding motifs is heterologous (optionally RSV P2B or a mutant thereof), (c) at least one of the two or more particle budding motifs comprises a PTAP motif, a PPPY motif, a PPXY motif, a YXXL motif, a YPXnL motif, or any combinations thereof, wherein n is an integer from 1 to 5, or (d) at least one of the two or more particle budding motifs comprises a sequence listed in Table 5. In some cases, the plasma membrane recruitment element comprises at least a portion of the P6 domain; optionally wherein the plasma membrane recruitment element comprises at least a N-terminal fragment of the P6 domain or at least a C-terminal fragment of the P6 domain; optionally wherein the plasma membrane recruitment element comprises the mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of HIV. In some cases, the plasma membrane recruitment element is fused to the post- translational modification motif is selected from the group consisting of: a myristoylation motif, an acetylation motif, an isoprenylation motif, a palmitoylation motif, and a famesylation motif. In some cases, the plasma membrane recruitment element comprises the two spacer peptides; optionally wherein at least one of the two spacer peptides is P2 domain or Pl domain; optionally wherein the two spacer peptides are P2 domain and P 1 domain; optionally wherein the plasma membrane recruitment element comprises the mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of HIV. In somecases, the recombinant protein further comprises the envelope protein, and wherein the envelope protein comprises the envelope protein from human endogenous retrovirus (HERV) or a mutant thereof; optionally wherein the envelope protein comprises hENVHl, hENVH2, hENVH3, hENVKl, hENVK2, hENVK3, hENVK4, hENVK5, hENVK6, hENVT, hENVW, hENVFRD, hENVR, hENVR(b), hENVR(c)2, hENVR(c) 1, or hENVKcon, or a mutant thereof. In some cases, the plasma membrane recruitment element is fused to the membrane penetrating peptide; optionally wherein the membrane penetrating peptide is linked to the plasma membrane recruitment element; optionally wherein the membrane penetrating peptide comprises a sequence having at least about 80% sequence identity to a sequence listed in Table 6. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of HIV and wherein (1) the plasma membrane recruitment element is fused to the cleavable linker or the membrane penetrating peptide; or (2) wherein the recombinant protein further comprises the envelope protein, wherein the envelope protein comprises the envelope protein from human endogenous retrovirus (HERV) or a mutant thereof. In some cases, the plasma membrane recruitment element comprises (a) at least a fragment of matrix protein of an HIV gag, optionally a N-terminal fragment of the matrix protein of the HIV gag; or (b) a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof. In some cases, the plasma membrane recruitment element comprises at least a fragment of capsid protein of the HIV gag; optionally wherein the plasma membrane recruitment element comprises a full-length capsid protein of the HIV gag; optionally wherein the plasma membrane recruitment element comprises a C-terminal fragment of capsid protein of the HIV gag. In some cases, the plasma membrane recruitment element comprises a spacer peptide of the HIV gag; optionally wherein the plasma membrane recruitment element comprises a P2 domain of the HIV gag, a Pl domain of the HIV gag, or both. In some cases, the plasma membrane recruitment element comprises (a) a heterologous domain, optionally wherein the heterologous domain comprises a multimerization motif, optionally wherein the multimerization motif forms parallel homodimers or parallel heterodimers (optional DZF), optionally wherein the parallel homodimers comprise a coiled-coil, optionally wherein the coiled-coil is a leucine zipper, optionally wherein the plasma membrane recruitment element lacks nucleocapsid protein of the HIV gag; or (b) a full-length nucleocapsid protein of the HIV gag or a fragment thereof. In some cases, the plasma membrane recruitment element comprises a particle budding motif; optionally wherein the plasma membrane recruitment element comprises two or more particle budding motifs; optionally wherein at least one of the particle budding motifs is (a) a particle budding motif of the HIV gag (optionally a N-terminal fragment of the P6 domain of the HIV gag, a PTAP motif, or a full-length P6 domain of the HIV gag); or (b) a heterologous particle budding motif (optionally RSV P2B or a mutant thereof or a sequence listed in Table 5). In some cases, the plasma membrane recruitment element lacks a matrix protein of the HIV gag and wherein the plasma membrane recruitment element comprises a N-terminal myristoylation motif, the full-length capsid protein of the HIV gag or a fragment thereof, the multimerization motif (optionally a DZF), and a heterologous particle budding motif (optionally a late domain of RSV) arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membranerecruitment element. In some cases, the plasma membrane recruitment element comprises (a) the N- terminal fragment of the matrix protein of the HIV gag or the pleckstrin homology (PH) domain or a mutant thereof; (b) the full-length capsid protein of the HIV gag or a fragment thereof; (c) optionally the P2 domain of the HIV gag; (d) the multimerization motif (optionally a leucine zipper) or the full-length nucleocapsid protein of the HIV gag or a fragment thereof; and (e) the particle budding motif; optionally wherein the (a)-(e) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the full- length capsid protein of the HIV gag or a fragment thereof, the P2 domain of the HIV gag, the full-length capsid protein of the HIV gag, the Pl domain of the HIV gag, and the P6 domain of the HIV gag or a fragment thereof, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the full- length capsid protein of the HIV gag or a fragment thereof, the P2 domain of the HIV gag, the leucine zipper, and the P6 domain of the HIV gag or a fragment thereof, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag or a fragment thereof, the P2 domain of the HIV gag, the leucine zipper, and a particle budding motif, arranged in order from a N- terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif, a C-terminal fragment of the HIV gag, the P2 domain of the HIV gag, the leucine zipper, and a second particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, optionally a first particle budding motif, the full- length capsid protein of the HIV gag or a fragment thereof, optionally the P2 domain of the HIV gag, the leucine zipper, and optionally a second particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the first and the second particle budding motif; optionally wherein each of the first and the second particle budding motifs independently (a) is the particle budding motif of the HIV gag; (b) is a heterologous particle budding motif (optionally RSV P2B or a mutant thereof); or (c) comprises a sequence listed in Table 5. In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the heterologous particle budding motif, the full-length capsid protein of the HIV gag, the P2 domain, the leucine zipper, and the particle budding motif of the HIV gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof. In somecases, the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag or the pleckstrin homology (PH) domain or a mutant thereof, the full-length capsid protein of the HIV gag, the P2 domain, the full-length nucleocapsid protein of the HIV gag, and the particle budding motif of the HIV gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof.

[0007] In some aspects, disclosed herein is a recombinant protein comprising a plasma membrane recruitment element comprising a mutant gag polyprotein that is not from HIV, and wherein the plasma membrane recruitment element lacks at least a fragment of a matrix protein, at least a fragment of a RNA- binding phosphoprotein, at least a fragment of a capsid protein, a gag -endogenous protease cleavage sequence, or at least a fragment of a nucleocapsid protein. In some cases, the mutant gag polyprotein is mutant of a wild-type gag polypeptide of a retrovirus; optionally wherein the retrovirus is oncoretroviruses, lentiviruses, or spumaviruses; optionally wherein the retrovirus is MMLV or RSV. In some cases, the mutant gag polyprotein is mutant of a wild-type gag polypeptide of a human endogenous retrovirus (HERV) or a gag homology protein (optionally human Arc); optionally wherein the HERV is HERV-K or HERV-W; optionally wherein the HERV-K is HERV-K113, HERV-K101, HERV-K102, HERV-K104, HERV-K107, HERV-K108, HERV-K109, HERV-K115, HERV-Kl lp22, or HERV- K12ql3; optionally wherein the mutant gag polyprotein is mutant of a wild-type gag polypeptide of HERV-K113 or a hGAGKcon. In some cases, the mutant gag polyprotein is mutant of a wild-type gag polypeptide of an alpharetrovirus, a betaretrovirus, or a deltaretrovirus, optionally the wild type gag polyprotein comprises the sequence set forth in any one of SEQ ID NOs: 285-298. In some cases, the at least a fragment of the matrix protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the matrix protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the matrix protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the matrix protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the RNA-binding phosphoprotein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the RNA-binding phosphoprotein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the RNA-binding phosphoprotein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the RNA-binding phosphoprotein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the capsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the capsid protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the capsid protein comprises at least 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the capsid protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the nucleocapsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the nucleocapsid protein of a corresponding wild type gag polyprotein. In some cases, the at least a fragment of the nucleocapsid protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the nucleocapsid protein of a corresponding wild type gag polyprotein. In some cases, the plasma membrane recruitment element lacks the at least a fragment of a matrix protein; optionally wherein the plasma membrane recruitment element lacks a N-terminal fragment of the matrix protein. In some cases, the plasma membrane recruitment element lacks the at least a fragment of a RNA-binding phosphoprotein; optionally wherein the plasma membrane recruitment element comprises a mutant of a wild-type gag polyprotein of MMLV. In some cases, the plasma membrane recruitment element lacks the at least a fragment of a capsid protein; optionally wherein the plasma membrane recruitment element lacks a N-terminal fragment of the capsid protein, a C-terminal fragment of the capsid protein, or both. In some cases, the plasma membrane recruitment element lacks the gag -endogenous protease cleavage sequence. In some cases, the plasma membrane recruitment element lacks the at least a fragment of a nucleocapsid protein; optionally wherein the plasma membrane recruitment element lacks a N-terminal fragment of the nucleocapsid protein, a C-terminal fragment of the nucleocapsid protein, or both; optionally wherein the plasma membrane recruitment element lacks the nucleocapsid protein. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of MMLV. In some cases, the plasma membrane recruitment element comprises (a) a matrix protein of the MMLV gag (optionally full-length matrix protein of the MMLV gag, a N-terminal fragment or a C-terminal fragment of the full-length matrix protein of the MMLV gag), a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof; (b) a capsid protein of the MMLV gag or a mutant thereof, optionally wherein the capsid protein of the MMLV gag or a mutant thereof is a full-length capsid protein of the MMLV gag, or a N-terminal fragment of or a C- terminal fragment of the full-length capsid protein of the MMLV gag; (c) heterologous domain, optionally wherein the heterologous domain comprises a multimerization motif (optionally a leucine zipper); and (d) an optional particle budding motif, optionally wherein the particle budding motif is particle budding motif of the MMLV gag; optionally wherein the particle budding motif is a heterologous particle budding motif; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof or a sequence listed in Table 5; optionally wherein the (a)-(d) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the plasma membrane recruitment element further comprises a P12 domain of the MMLV gag or a mutant thereof located between (a) and (b), optionally wherein the P12 domain of the MMLV gag or a mutant thereof is a full-length P12 domain of the MMLV gag, a N-terminal fragment of the full-length P12 domain of the MMLV gag, a C-terminal fragment of the full- length P12 domain of the MMLV gag, or a fragment of the full-length P12 domain of the MMLV gag fused to a heterologous particle budding motif (optionally RSV P2B or a mutant thereof or a sequence listed in Table 5). In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the full-length matrix protein of the MMLV gag, the full-length P12 domain of the MMLV gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the MMLV gag or a fragment thereof, and the leucine zipper, arranged in order from a N- terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length P12 domain of the MMLV gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the MMLV gag or a fragment thereof, the leucine zipper, and optionally the particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the full-length matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag or a fragment thereof, the leucine zipper, and the particle budding motif, arranged in order from a N- terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length capsid protein of the MMLV gag or a fragment thereof, the leucine zipper, and the particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of hGAGKcon; optionally wherein the plasma membrane recruitment element comprises a matrix protein of the RSV gag and a late domain of the RSV gag; optionally wherein the plasma membrane recruitment element comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a full-length nucleocapsid protein of the RSV gag; optionally wherein the plasma membrane recruitment element comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a fragment of the nucleocapsid protein of the RSV; optionally wherein the plasma membrane recruitment element further comprises a N-terminal myristoylation motif of the RSV gag. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of HERV-K113. In some cases, the plasma membrane recruitment element comprises (a) a matrix protein of the HERV-K113 gag (optionally full-length matrix protein of the HERV-K113 gag, a N-terminal fragment or a C-terminal fragment of the full-length matrix protein of the HERV-K113 gag), a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof; (b) a capsid protein of the HERV-K113 gag or a mutant thereof, optionally wherein the capsid protein of the HERV-K113 gag or a mutant thereof is a full-length capsid protein of the HERV-K113 gag, or a N-terminal fragment of or a C-terminal fragment of the full-length capsid protein of the HERV-K113 gag; (c) heterologous domain, optionally wherein the heterologous domain comprises a multimerizationmotif (optionally a leucine zipper); and (d) an optional particle budding motif, optionally wherein the particle budding motif is particle budding motif of the HERV-K113 gag; optionally wherein the particle budding motif is a heterologous particle budding motif; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof or a sequence listed in Table 5); (e) an optional QP1 domain of the HERV-K113 gag; and (f) an optional QP2 domain of the HERV-K113 gag; optionally wherein (a)-(f) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the plasma membrane recruitment element further comprises a P15 domain of the HERV-K113 gag or a mutant thereof, optionally wherein the P 15 domain of the HERV-K113 gag or a mutant thereof is a full-length P15 domain of the HERV-K113 gag, a N-terminal fragment of the full-length P15 domain of the HERV-K113 gag, a C-terminal fragment of the full-length P15 domain of the HERV-K113 gag, or a fragment of the full-length P15 domain of the HERV-K113 gag fused to a heterologous particle budding motif (optionally RSV P2B or a mutant thereof or a sequence listed in Table 5). In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the full-length matrix protein of the HERV- K113 gag, the full-length P15 domain of the HERV-K113 gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, the optional QP1 domain of the HERV-K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length P15 domain of the HERV-K113 gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, optionally the particle budding motif, the optional QP1 domain of the HERV- K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the N-terminal fragment of the full- length matrix protein of the HERV-K113 gag, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, the particle budding motif, the optional QP1 domain of the HERV- K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, the particle budding motif, the optional QP1 domain of the HERV-K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises the QP 1 domain and the QP2 domain of the HERV-K113 gag. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of RSV; optionally wherein the mutant gagpolyprotein comprises a matrix protein of the RSV gag and a late domain of the RSV gag; optionally wherein the mutant gag polyprotein comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a full-length nucleocapsid protein of the RSV; optionally wherein the mutant gag polyprotein comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a fragment of the nucleocapsid protein of the RSV; optionally wherein the mutant gag polyprotein comprises a N-terminal myristoylation motif of the RSV gag. In some cases, the plasma membrane recruitment element comprises one, two, or three particle budding motif, wherein each of the particle budding motif is selected from a sequence listed in Table 5. In some cases, the plasma membrane recruitment element comprises a MHR. In some cases, the plasma membrane recruitment element comprises the heterologous sequence; optionally wherein the heterologous sequence is fused to at least a fragment of the matrix protein, optionally the N-terminal of the fragment of the matrix protein; optionally wherein the heterologous sequence is a pleckstrin homology (PH) domain or a mutant thereof; optionally wherein the PH domain is a human PH domain; optionally wherein the fragment of the matrix protein lacks a N-terminal myristoylation motif, a N-terminal glycine, a highly basic region (HBR), a N-terminal fragment, or any combinations thereof. In some cases, the plasma membrane recruitment element further comprises one or more mutant gag -endogenous protease cleavage sequences relative to a corresponding wildtype gag- endogenous protease cleavage sequence, and wherein the one or more mutant gag-endogenous protease cleavage sequences have higher cleavage efficiency than that of the corresponding wildtype gag- endogenous protease cleavage sequence.

[0008] In some aspects, disclosed herein is a chimeric protein comprising the recombinant protein described herein, wherein the chimeric protein comprises a cleavable linker; optionally wherein the cleavable linker connects the plasma membrane recruitment element and a payload.In some cases, the chimeric protein comprises a nuclear localization signal (NLS) sequence. In some cases, the chimeric protein comprises a nuclear export signal (NES) sequence. In some cases, the chimeric protein comprises the membrane penetrating peptide, optionally wherein (a) the membrane penetrating peptide is linked to the payload or the plasma membrane recruitment element; or (b) the membrane penetrating peptide connects the payload and the plasma membrane recruitment element; optionally wherein the membrane penetrating peptide comprises a sequence having at least about 80% sequence identity to a sequence listed in Table 6. In some cases, the chimeric protein comprises a post- translational modification motif that is fused directly to (a) the payload; or (b) the plasma membrane recruitment element; optionally wherein the post-translational modification motif comprises a myristoylation motif, an acetylation motif, an isoprenylation motif, a palmitoylation motif, a famesylation motif, or combinations thereof. In some cases, the chimeric protein comprises the plasma membrane recruitment element, an optional NLS, the cleavable linker, and the payload arranged in order from N- terminus of the chimeric protein to C-terminus of the chimeric protein. In some cases, the payload comprises an antibody, a cytokine, a therapeutic protein, a small molecule therapeutics, a therapeutic DNA, and a therapeutic RNA, a ribonucleoprotein, a zinc-finger, a transcription activator-like effector(TALE), or a CRISPR-based genome editor, or any combinations thereof; optionally wherein the payload comprises a NLS, optionally wherein the NLS is an endogenous NLS or a heterologous NLS.

[0009] In some aspects, disclosed herein is a composition comprising a first nucleic acid sequence encoding the recombinant protein described herein or the chimeric protein described herein.In some cases, the composition comprises a second nucleic acid sequence encoding an envelope protein; optionally wherein the envelope protein is a retroviral envelope protein or a mutant thereof; optionally wherein the envelope protein is an envelope protein from human endogenous retrovirus (HERV) or a mutant thereof. In some cases, the composition further comprises a third nucleic acid sequence encoding a second plasma membrane recruitment element; optionally wherein the second plasma membrane recruitment element is the same as the plasma membrane recruitment element; optionally wherein the second plasma membrane recruitment element is a retroviral gag or a mutant thereof, a HERV gag or a mutant thereof, a pleckstrin homology (PH) domain or a mutant thereof, or a membrane protein or a transmembrane domain thereof or a mutant thereof. In some cases, the composition further comprises fourth nucleic acid encoding a protease; optionally wherein the protease is a retroviral protease. In some cases, the plasma membrane recruitment element is linked to the protease, optionally via a cleavable linker. In some cases, the second plasma membrane recruitment element is linked to the protease, optionally via a cleavable linker.

[0010] In some aspects, disclosed herein is a system comprising the lipid delivery particle described herein or the composition described herein. In some cases, the system comprises a producer cell, a cell- free extract, or a cell lysate.

[0011] In some aspects, disclosed herein is a pharmaceutical composition comprising (a) the lipid delivery particle described herein or the system described herein; and (b) a pharmaceutically acceptable excipient.

[0012] In some aspects, disclosed herein is a kit comprising (a) the lipid delivery particle described herein, the system described herein, or the pharmaceutical composition described herein; and (b) an information material containing instructions for administering a dosage of the lipid delivery particle or the system, or a dosage form of the pharmaceutical composition to a subject.

[0013] In some aspects, disclosed herein is a method of treating a disease or a condition in a subject in need thereof, comprising administering to the subject the lipid delivery particle described herein, the system described herein, or the pharmaceutical composition described herein.

[0014] In some aspects, disclosed herein is a method comprising contacting a cell with the lipid delivery particle described herein.

[0015] In some aspects, disclosed herein is a method comprising contacting a cell with the system described herein.

[0016] In some aspects, disclosed herein is a method comprising administering the lipid delivery particle described herein, the system described herein, or the pharmaceutical composition described herein to a subject in need thereof.

[0017] In some aspects, disclosed herein is a method of producing the lipid delivery particle described herein. In some cases, the method comprises contacting a producer cell with the composition described herein.INCORPORATION BY REFERENCE

[0018] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The novel features of the disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings of which:

[0020] FIG. 1A depicts schematic representations of exemplary plasma membrane recruitment element constructs that comprise a mutant Moloney Murine leukemia virus (MMLV) gag as compared to wildtype MMLV gag according to some embodiments of the present disclosure. The schematics showing various domains of MMLV gag, truncations thereof, or replacement or fusion of a domain with another protein are for illustrative purporses only and does not represent the actual length or the relative size of one domain as compared to another domain. In some cases, the cleavage sequences can be mutated to eliminate proteolysis.

[0021] FIG. IB depicts schematic representations of exemplary plasma membrane recruitment element constructs that comprise a mutant Moloney Murine leukemia virus (MMLV) gag as compared to wildtype MMLV gag according to some embodiments of the present disclosure. The schematics showing various domains of MMLV gag, truncations thereof, or replacement or fusion of a domain with another protein are for illustrative purporses only and does not represent the actual length or the relative size of one domain as compared to another domain. In some cases, the cleavage sequences can be mutated to promote proteolysis.

[0022] FIG. 2A depicts schematic representations of exemplary plasma membrane recruitment element constructs that comprise a mutant Human Endogenous Retrovirus (HERV) K-l 13 gag as compared to wild-type HERV-K113 gag according to some embodiments of the present disclosure. The schematics showing various domains of HERV-K113 gag, truncations thereof, or replacement or fusion of a domain with another protein are for illustrative purporses only and does not represent the actual length or the relative size of one domain as compared to another domain. In some cases, the cleavages sequence can be mutated to eliminate proteolysis.

[0023] FIG. 2B depicts schematic representations of exemplary plasma membrane recruitment element constructs that comprise a mutant Human Endogenous Retrovirus (HERV) K-l 13 gag as compared to wild-type HERV-K113 gag according to some embodiments of the present disclosure. The schematicsshowing various domains of HERV-K113 gag, truncations thereof, or replacement or fusion of a domain with another protein are for illustrative purporses only and does not represent the actual length or the relative size of one domain as compared to another domain. In some cases, the cleavage sequences can be mutated to promote proteolysis.

[0024] FIG. 3A depicts schematic representations of exemplary plasma membrane recruitment element constructs that comprise a mutant Human Immunodeficiency Virus (HIV) gag as compared to wild-type HIV gag according to some embodiments of the present disclosure. The schematics showing various domains of HIV gag, truncations thereof, or replacement or fusion of a domain with another protein are for illustrative purporses only and does not represent the actual length or the relative size of one domain as compared to another domain. In some cases, the cleavage sequences can be mutated to eliminate proteolysis.

[0025] FIG. 3B depicts schematic representations of exemplary plasma membrane recruitment element constructs that comprise a mutant Human Immunodeficiency Virus (HIV) gag as compared to wild-type HIV gag according to some embodiments of the present disclosure. The schematics showing various domains of HIV gag, truncations thereof, or replacement or fusion of a domain with another protein are for illustrative purporses only and does not represent the actual length or the relative size of one domain as compared to another domain. In some cases, the cleavage sequences can be mutated to promote proteolysis.

[0026] FIG. 4 depicts schematic representations of exemplary plasma membrane recruitment element constructs named RSV ML, RSV MLNC Large, and RSV MLNC Small listed in the Table 10B.

[0027] FIG. 5 depicts schematic representations of exemplary plasma membrane recruitment element constructs named RSV Myr LNC Large and RSV Myr LNC Small listed in the Table 10B.

[0028] FIG. 6 depicts schematic representations of exemplary plasma membrane recruitment element constructs named PH-RSV LNC Large, PH-RSV LNC Small, and HIV CAP dDZFl listed in the Table 10B

[0029] FIG. 7 depicts schematic representations of exemplary plasma membrane recruitment element constructs named HIV CAP dDZF2, hGAGKcon Large CAP dDZFl, and hGAGKcon Large CAP dDZF2 listed in the Table 10B.

[0030] FIG. 8 depicts schematic representations of exemplary plasma membrane recruitment element constructs named hGAGKcon Small CAP dDZFl and hGAGKcon Small CAP dDZF2 listed in the Table10B

[0031] FIG. 9 depicts schematic representations of exemplary plasma membrane recruitment element constructs named hGAGKcon Smallv2 CAP dDZFl and hGAGKcon Smallv2 CAP dDZF2 listed in the Table 10BDETAILED DESCRIPTION

[0032] The practice of some methods disclosed herein employ, unless otherwise indicated, conventional techniques of immunology, biochemistry, chemistry, molecular biology, microbiology, cell biology,genomics and recombinant DNA, which are within the skill of the art. See for example Sambrook and Green, Molecular Cloning: A Laboratory Manual, 4th Edition (2012); the series Current Protocols in Molecular Biology (F. M. Ausubel, et al. eds.); the series Methods In Enzymology (Academic Press, Inc.), PCR 2: A Practical Approach (M.J. MacPherson, B.D. Hames and G.R. Taylor eds. (1995)), Harlow and Lane, eds. (1988) Antibodies, A Laboratory Manual, and Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, 6th Edition (R.I. Freshney, ed. (2010)).

[0033] Viral-like particles (VLPs) are nanoscale structures comprising assembled proteins (e.g., viral components, such as structural proteins) that lack viral genetic material. VLPs can be generated from gag- pro-pol polyproteins that are retroviral, lentiviral, or endogenous (e.g., from human, such as human endogenous retrovirus). Expression of the viral components can occur in various living or cell-free expression systems, then the viral components can self-assemble and reconstruct into lipid particles. The expression of viral components through gag-pro-pol genes utilizes weak terminators or ribosomal framshifting or both for expressing gag, pro, and pol proteins. Payloads can be efficiently captured in VLPs by fusing to a gag polyprotein (i.e., forms a chimeric protein) for protein payloads or a other non- covalent binding mechanisms (e.g., gag fused to an RNA-binding protein that can bind an RNA sequence located on the payload). After the VLPs are delivered to a target cell, the payloads can be liberated from the VLPs after membrane fusion, and in some cases, after a protease cleaves a cleavable linker between the payload and the rest of the fusion protein.

[0034] Without wishing to be bound by a certain theory, the present disclosure provides improved VLPs with higher capacity of payload delivery and reduced immunogenity by modification of the components within the VLPs (e.g, a plasma membrane reruitment element comprising a mutant gag polyprotein). By utilitzing a mutant gag polyprotein as part of the plasma membrane recruitment element, such as a mutant gag with smaller size and domain swaps (e.g., swapping a nucleocapsid with a multimerization motif, such as a leucine zipper), there can be potentials for improvement in various aspects. For instance, by removing certain domains within a gag, there can be reduced packing of undesirable molecules (e.g., non- therapeutic molecules, non-specific mRNA or pDNA). Smaller total DNA sequence can allow high RNA or protein expression, for example, via higher total DNA delivery, which can offer potential for titer increase. There can be more room for payload as the size of plasma membrane recruitment element is reduced. Truncation in capsid protein can eliminate the formation of capsid cage that can sequester payloads and prevent release of the payloads upon delivery to a target cell, both of which can lead to higher encapsulation rate per particle, better release of payload in a target cell, or higher instrinsic activity. There is also potential for biodiversity advantage as the particles generated can have a smaller size. Introducing a fusion of a plasma membrane recruitment element and a protease can permit increased release and downstream activity of the payload after being delivered to a target cell. Additional modifications of the plasma membrane recruitment element or a chimeric protein comprising the plasma membrane recruitment element can include introducing additional particle budding motifs (e.g., either homologous or heterologous) to drive better budding of the particle in a producer cell, fusing a Pleckstrinhomology (PH) domain to the N-terminus of the mutant gag, or synthetic sequences with other advantages (e.g., less immunogenecity to human subjects).

[0035] Disclosed herein, in some aspects, are lipid delivery particles comprising a lipid membrane. In some cases, the membrane encapsulates a payload. In some cases, the lipid delivery particle comprises a plasma membrane recruitment element comprising a mutant gag polyprotein, and a payload within the cavity. In some cases, the plasma membrane recruitment element lacks at least a fragment of a matrix protein, at least a fragment of a RNA-binding phosphoprotein, at least a fragment of a capsid protein, a gag -endogenous protease cleavage sequence, or at least a fragment of a nucleocapsid protein. In some cases, the mutant gag polyprotein is not from HIV. In some cases, the plasma membrane recruitment element comprises (i) a full-length capsid protein; (ii) a full-length matrix protein; (iii) a heterologous sequence; (iv) at least a portion of a nucleocapsid protein; (v) two or more particle budding motifs; (vi) at least a portion of a P6 domain; or (vii) two spacer peptides. In some cases, the lipid delivery particle further comprises an envelope protein, wherein the envelope protein comprises an envelope protein from human endogenous retrovirus (HERV) or a mutant thereof. In some cases, the plasma membrane recruitment element is fused to (i) a cleavable linker; (ii) a membrane penetrating peptide; or (iii) a post- translational modification motif.

[0036] Disclosed herein, in some aspects, is a recombinant protein comprising a plasma membrane recruitment element comprising a mutant gag polyprotein. In some cases, the plasma membrane recruitment element lacks at least a fragment of a matrix protein, at least a fragment of a RNA-binding phosphoprotein, at least a fragment of a capsid protein, a gag-endogenous protease cleavage sequence, or at least a fragment of a nucleocapsid protein. In some cases, the mutant gag polyprotein is not from HIV. In some cases, the plasma membrane recruitment element comprises (i) a full-length capsid protein; (ii) a full-length matrix protein; (iii) a heterologous sequence; (iv) at least a portion of a nucleocapsid protein; (v) two or more particle budding motifs; (vi) at least a portion of a P6 domain; or (vii) two spacer peptides. In some cases, the plasma membrane recruitment element is fused to (i) a cleavable linker; (ii) a membrane penetrating peptide; or (iii) a post-translational modification motif.

[0037] Also disclosed herein are chimeric proteins comprising the recombinant protein described herein and a cleavable linker. In some cases, the cleavable linker connects the plasma membrane recruitment element and a payload.

[0038] Also disclosed herein is a composition comprising nucleic acid sequences encoding the components within the lipid delivery particles. In some cases, the compostion comprises a first nucleic acid sequence encoding the recombinant protein described herein or the chimeric protein described herein. In some cases, the composition comprises a second nucleic acid sequence encoding an envelope protein. In some cases, the envelope protein is a retroviral envelope protein or a biologically mutant thereof. In some cases, the envelope protein is an envelope protein from human endogenous retrovirus (HERV) or a biologically active mutant thereof.

[0039] Also disclosed herein is a system, a pharmaceutical composition, a kit, method of using and making relating to the lipid delivery particle, the recombinant protein, or the chimeric protein described herein.

[0040] Without wishing to be bound by a certain theory, presence of one or more of (i) a particle budding motif; (ii) a membrane penetrating peptide motif; or (iii) a post-translational modification motif in the chimeric protein of the present disclosure can improve production of the lipid delivery particles, as well as the incorporation of lipid delivery particles into their appropriate target. In some cases, additional motifs are present in the chimeric protein of the lipid delivery particle. The motifs of the present disclosure can also include polypeptide sequences that are additionally fused to the fusion of the plasma membrane recruitment element and the payload, or in some cases replacing or modifying elements of the fusion of the plasma membrane recruitment element and payload. The plasma membrane recruitment elements and motifs can be placed at the N-terminus, C-terminus, or between the N- and C-terminus of the construct. In some cases, the plasma membrane recruitment elements and motifs can be present in repeating fashion (in tandem) or at various segments of the DNA.DEFINITIONS

[0041] Certain specific details of this description are set forth in order to provide a thorough understanding of various embodiments. However, one skilled in the art will understand that the present disclosure may be practiced without these details. In other instances, well-known structures have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the disclosure.

[0042] Unless the context requires otherwise, throughout the specification and claims which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense, that is, as “including, but not limited to.” Further, headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed disclosure.

[0043] As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. The use of the words “a” or “an” when used in conjunction with the term “comprising” herein may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.”

[0044] It should also be noted that the term “or” is generally employed in its sense including “and / or” unless the content clearly dictates otherwise.

[0045] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below.

[0046] The term “about” when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20% or in some instances ±10%, or in some instances ±5%, or in some instances ±1%, or in some instances ±0. 1% from the specified value, as such variations are appropriate to perform the disclosed methods. As used herein, “about” and “approximately” generally mean an acceptable degree of error for the quantity measured given the nature or precision of themeasurements. Exemplary degrees of error are within 20 percent (%), typically, within 10%, and more typically, within 5% of a given range of values.

[0047] Calculations of homology or sequence identity between sequences (the terms are used interchangeably herein) are performed as follows. To determine the percent identity of two amino acid sequences, or of two nucleic acid sequences, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment and non-homologous sequences can be disregarded for comparison purposes). In some cases, the length of a reference sequence aligned for comparison purposes is at least 30%, preferably at least 40%, more preferably at least 50%, 60%, and even more preferably at least 70%, 80%, 90%, 100% of the length of the reference sequence. The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position (as used herein amino acid or nucleic acid “identity” is equivalent to amino acid or nucleic acid “homology”).

[0048] The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. In some cases, the percent identity between two amino acid sequences is determined using the Needleman and Wunsch ((1970) J. Mol. Biol. 48:444-453 ) algorithm which has been incorporated into the GAP program in the GCG software package (available at http: / / www.gcg.com), using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. In some cases, the percent identity between two nucleotide sequences is determined using the GAP program in the GCG software package (available at http: / / www.gcg.com), using a NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6. A particularly preferred set of parameters (and the one that should be used unless otherwise specified) are a Blossum 62 scoring matrix with a gap penalty of 12, a gap extend penalty of 4, and a frameshift gap penalty of 5.

[0049] The percent identity between two amino acid or nucleotide sequences can be determined using the algorithm of E. Meyers and W. Miller ((1989) CABIOS, 4: 11-17) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. The nucleic acid and protein sequences described herein can be used as a “query sequence” to perform a search against public databases to, for example, identify other family members or related sequences. Such searches can be performed using the NBLAST and XBLAST programs (version 2.0) of Altschul, et al. (1990) J. Mol. Biol. 215:403-10. BLAST nucleotide searches can be performed with the NBLAST program, score = 100, wordlength = 12 to obtain nucleotide sequences homologous to a nucleic acid molecule of the disclosure. BLAST protein searches can be performed with the XBLAST program, score = 50, wordlength = 3 to obtain amino acid sequences homologous to protein molecules ofthe disclosure. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al., (1997) Nucleic Acids Res. 25:3389-3402. When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used.

[0050] It is understood that the molecules of the present disclosure may have additional conservative or non-essential amino acid substitutions, which do not have a substantial effect on their functions.

[0051] The terms “peptide,” “polypeptide,” and “protein” are used interchangeably, and refer to a compound comprised of amino acid residues covalently linked by peptide bonds. A protein or peptide must contain at least two amino acids, and no limitation is placed on the maximum number of amino acids that can comprise a protein’s or peptide’s sequence. Polypeptides include any peptide or protein comprising two or more amino acids joined to each other by peptide bonds. As used herein, the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types. “Polypeptides” include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others. A polypeptide includes a natural peptide, a recombinant peptide, or a combination thereof.

[0052] The term “expression vector” refers to a vector comprising a recombinant polynucleotide comprising expression control sequences operatively linked to a nucleotide sequence to be expressed. An expression vector comprises sufficient cis-acting elements for expression; other elements for expression can be supplied by the host cell or in an in vitro expression system. Expression vectors include all those known in the art, including cosmids, plasmids (e.g., naked or contained in liposomes) and viruses (e.g., lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses) that incorporate the recombinant polynucleotide.

[0053] The term “promoter” refers to a DNA sequence recognized by the transcription machinery of the cell, or introduced synthetic machinery, required to initiate the specific transcription of a polynucleotide sequence.

[0054] An example of a promoter is the immediate early cytomegalovirus (CMV) promoter sequence. This promoter sequence is a strong constitutive promoter sequence capable of driving high levels of expression of any polynucleotide sequence operatively linked thereto. In some cases, a polynucleotide comprises a CMV promoter. In some cases, a polynucleotide may comprise a promoter selected from the group consisting of, but not limited to, a simian virus 40 (SV40) early promoter, a mouse mammary tumor virus (MMTV), a human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, a MoMuLV promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter, a Rous sarcoma virus (RSV) promoter, an actin promoter, a myosin promoter, an elongation factor- la promoter, a hemoglobin promoter, and a creatine kinase promoter. In some cases, a polynucleotide comprises a sequence encoding a poly(A) tail. In some cases, a polynucleotide comprises a 3’ UTR sequence. In some cases, a polynucleotide comprises a 5’ UTR sequence. In some cases, a polynucleotidecomprises multiple smaller and discrete nucleotide sequences that are typically heterologous and exhibit different and measurable function(s), a promoter sequence, a translation initiating sequence, a start codon, a polyadenylation sequence, a stop codon, and / or a linker sequence.

[0055] The term “subject” is intended to include living organisms in which an immune response can be elicited (e.g., mammals, human). Exemplary subjects include humans, monkeys, dogs, cats, mice, rats, cows, horses, camels, goats, rabbits, and sheep. In certain embodiments, the subject is a human. A “patient” is a subject suffering from or at risk of developing a disease, disorder or condition or otherwise in need of the compositions and methods provided herein.

[0056] The term “therapeutic” as used herein means a treatment. A therapeutic effect is obtained by reduction, suppression, remission, or eradication of a disease state.

[0057] The term “prophylaxis” as used herein means the prevention of or protective treatment for a disease or disease state.

[0058] The term “transfected” or “transformed” or “transduced” refers to a process by which exogenous nucleic acid is transferred or introduced into the host cell. A “transfected” or “transformed” or “transduced” cell is one which has been transfected, transformed or transduced with exogenous nucleic acid. The cell includes the primary subject cell and its progeny. The term “transformed cell” or “transfected cell” can be a transformed or transfected cell in which inserted DNA can replicate either as an autonomously replicating plasmid or as part of the host chromosome. In some cases, a transfected cell or transformed cell can express the inserted DNA or RNA transiently (e.g., for brief periods of time).

[0059] The terms “nucleic acid,” “nucleic acid sequence,” “nucleotide sequence,” or “polynucleotide sequence,” and “polynucleotide” are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxy ribonucleotides or ribonucleotides, or analogs thereof. The polynucleotide may be either single -stranded or double -stranded, and if single-stranded may be the coding strand or noncoding (antisense) strand. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs. The sequence of nucleotides may be interrupted by non-nucleotide components. A polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component. The nucleic acid may be a recombinant polynucleotide, or a polynucleotide of genomic, cDNA, semisynthetic, or synthetic origin which either does not occur in nature or is linked to another polynucleotide in a non-natural arrangement.

[0060] The term “cell line” or “producer cell line”, as used herein, refers to cultured cells that can be passed (e.g., divided) more than once. In some cases, a cell like can be passed more than 2 times, more than 5 times, more than 10 times, more than 50 times, more than 100 times, or more than 150 times. In some cases, a cell line can be passed between 2-250 times. In some cases, a cell line can be passed up to 200 times.

[0061] The term “lipid delivery particle” refers to lipid vesicles secreted by the plasma membrane of a cell having a membrane or envelope that surrounds a central internal space. Lipid delivery particles can be produced via budding out of the cell’s plasma membrane, secretion from lysosomes, or export by the Golgi complex. Lipid delivery particles can promote intercellular communication in vitro and in vivo.Exemplary lipid delivery particles can include, but are not limited to, exosomes, ectosomes (e.g., microvesicles and shedding vesicles), apoptotic bodies, microsomes, micelles, oncosomes, and liposomes.

[0062] Lipid delivery particles can have a range of size, such as a cross-sectional diameter, wherein the cross-sectional diameter has a range from about 1 nm to about 1200 nm, about 10 nm to about 1200 nm, about 25 nm to about 1200 nm, about 50 nm to about 1200 nm, about 100 nm to about 1200 nm, about 10 nm to about 1000 nm, about 25 nm to about 1000 nm, about 50 nm to about 1000 nm, about 100 nm to about 1000 nm, about 10 nm to about 500 nm, about 25 nm to about 500 nm, about 50 nm to about 500 nm or about 100 nm to about 500 nm (all inclusive). Lipid delivery particles can comprise a vesicle size of greater than 10 nm. Lipid delivery particles can comprise a vesicle size of less than 1000 nm.

[0063] The term “module” or “modification”, used interchangeably, can refer to an addition or a motif that is added to a payload or a chimeric protein within lipid delivery particles (e.g., extracellular vesicles and / or virus-like particles). The additions can enhance characteristics of particle assembly and / or payload recruitment. A module can occur in combination or alone. A module can be linked to a payload or another element (e.g., domain) in a construct.

[0064] The term “purifying,” “purified,” and “purify,” can be used interchangeably and refer to a preparation phase of a lipid delivery particle. A preparation of lipid delivery particles can comprise a known or unknown concentration of a substance. In some cases, purifying produced lipid delivery particles comprises removing, either partially removing or wholly removing, a portion of the produced lipid delivery particles from a sample containing one or more biological components (e.g., producer cells). In some cases, a composition comprising lipid delivery particles, as described herein, that have been purified are enriched as compared to a starting sample. Enrichment of the lipid delivery particles can comprise 5%, 10%, 25%, 50%, 75%, 80%„ 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% enrichment compared to a starting sample. In some cases, purified lipid delivery particles can be free or substantially free of residual biological products. Residual biological products can include, but are not limited to, unwanted nucleic acids, proteins, lipids, and / or or metabolites or abiotic materials such as including chemicals. In some cases, lipid delivery particles free of residual biological products comprise lipid delivery particles containing no detectable producer cells in the composition.

[0065] The terms "portion" and "fragment" are used interchangeably herein and refer to a continuous element. Lor example, a part of a structure such as an amino acid sequence or protein refers to a continuous element of said structure. A portion, or a fragment of a structure preferably comprises one or more functional properties of said structure. In some cases, a portion, or a fragment of a structure such as an amino acid sequence comprises of at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% of the entire structure or amino acid sequence. In some cases, a portion, or a fragment of a structure such as an amino acid sequence comprises of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the entire structure or amino acid sequence. In some cases, a portion or a fragment can be proteins having at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99,100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more amino acids absent from the amino and / or carboxyl terminus of the amino acid sequence when compared to the reference amino acid sequence, optionally wherein the fragment has the same activity as the reference protein.

[0066] Ranges: throughout this disclosure, various aspects of the present disclosure can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the present disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. As another example, a range such as 95-99% identity, includes something with 95%, 96%, 97%, 98% or 99% identity, and includes subranges such as 96-99%, 96-98%, 96-97%, 97-99%, 97-98% and 98-99% identity. This applies regardless of the breadth of the range.LIPID DELIVERY PARTICLE

[0067] In an aspect, described herein is a lipid delivery particle comprising a plasma membrane recrtuiment element that comprises a mutant gag polyprotein for delivery of a payload to a target cell. The chimeric protein can promote targeting of a payload to a recipient cell (e.g., target cell). The lipid delivery particle can comprise a virus like particle (VLP) or an extracellular vesicle secreted by a cell. A lipid delivery particle can be secreted by cells in vivo or if cultured in vitro. Following secretion, the lipid delivery particle can deliver a payload and release its components into a recipient cell. In some cases, the lipid delivery particle can comprise a VLP, an exosome, an ectosome (e.g., a microvesicle or a shedding vesicle), an apoptotic body, a microsome, a micelle, an oncosome, or a liposome. In some cases, the lipid delivery particle can comprise a nanoparticle.

[0068] Virus-like particles (VLPs) can be assemblies of viral proteins that can infect cells but lack viral general material. VLPs can be synthesized through expression of viral structural proteins. VLPs can be formed in vivo through assembly inside a producer cell via recombinant protein expression or in vitro through self-assembly in a vessel using quantities of purified protein. VLPs can be designed to deliver payloads to targeted cells and tissues. VLPs can be used to deliver to a recipient cell an agent (e.g., prophylactic agent, therapeutic agent or diagnostic agent) or an enclosed circular or linear DNA or RNA molecule.

[0069] Ectosomes can be small heterogenous membrane-bound particles that are shed from the surface of the cell membrane in the extracellular space. Ectosomes can be shed by budding or outward blebbing from the plasma membrane of the cell. Ectosomes can be shed from plasma membrane micro-domains (e.g., lipid rafts or caveolae domains). Ectosomes have a series of biological functions, including, but not limited to, regulation of nucleic acid metabolism, signal transduction, transport, protein metabolism, intercellular communication, apoptpsis, and cell growth. As described herein, ectosomes can comprise a payload that can be delivered to a target cell. Ectosomes can be variable in size. In some cases, anectosome can be between 25 and 1000 nm. In some cases, the ecostome can be about 30 nm, about 50 nm, about 75 nm, about 100 nm, about 200 nm, about 300 nm, about 400 nm, about 500 nm, about 600 nm, about 700 nm, about 800 nm, about 900 nm, or about 1000 nm in size.

[0070] Exosomes can be small vesicular particles formed by intraluminal vesicles within multivesicular bodies. Exosome can range from about 30- about 125 nm. In some cases, an exosome is about 30 nm, about 40 nm, about 50 nm, about 55 nm, about 60 nm, about 65 nm, about 70 nm, about 75 nm, about 80 nm, about 85 nm, about 90 nm, about 95 nm, or about 100 nm in size. Formation of exosomes can be regulated via the endosomal sorting complex required for transport (ESCRT), and / or by non-ESCRT- related mechanisms, including tetraspanins and membrane lipids.

[0071] Nanoparticles can be synthesized particles between about 1 and about 200 nm in size that can encapsulate payload for delivery to a recipient cell. In some cases, nanoparticles are engineered for a specific cell type and trigger endocytosis and later endosome lysis. In some cases, a nanoparticle is about 5 nm, about 10 nm, about 15 nm, about 20 nm, about 25 nm, about 30 nm, about 35 nm, about 40 nm, about 45 nm, about 50 nm, about 60 nm, about 70 nm, about 80 nm, about 90 nm, or about 100 nm in size. In some cases, a nanoparticle can be about 105 nm, about 110 nm, about 115 nm, about 120 nm, about 125 nm, about 130 nm, about 135 nm, about 140 nm, about 145 nm, about 150 nm, about 160 nm, about 170 nm, about 180 nm, about 190 nm, or about 200 nm in size (e.g., a diameter). Without wishing to be bound by a theory, the small size can allow a higher intracellular uptake compared to larger molecules.ENVELOPE PROTEIN

[0072] In some aspects, the lipid delivery particle provided herein comprises an envelope protein. The envelope protein can be associated with the outside boundary or the surface of the lipid delivery particle, for example, the membrane or envelope of the lipid delivery particle.

[0073] The membrane of the lipid delivery particle can comprise a lipid layer, such as a single layer or a lipid bilayer. In some cases, the membrane of the lipid delivery particle is from plasma membrane, endoplasmic reticulum, or a combination thereof. In some cases, the membrane of the lipid delivery particle is from Golgi complex, ER Golgi intermediate compartment, or nuclear envelope. In some cases, the membrane of the lipid delivery particle is from plasma membrane. In some cases, the membrane of the lipid delivery particle is a phospholipid bilayer.

[0074] The envelope protein can be associated with the membrane of the lipid delivery particle in various manners. For example, the envelope protein can be anchored or attached to the external membrane of the particle, or anchored or attached to the internal membrane of the particle. The envelope protein can be embedded or inserted in the membrane, spanning through the membrane, with certain portions located at the outside of the membrane, or certain portions extending to the inside of the particle, or both. The envelope protein within the lipid delivery particle described herein can be overexpressed from an exogenous source, such as plasmids or stably integrated transgenes, in the production cells.

[0075] The envelope protein can play a role in the delivery of the lipid delivery particle to a target cell and release of the components of the lipid delivery particle within the target cell. The envelope protein can contact with the surface of a target cell and participate in the fusion of the lipid delivery particle and the membrane of the target cell. The envelope protein can participate in the fusion of the lipid delivery particle with the membrane of the target cell via any appropriate mechanism, such as those described in White et al. Crit Rev Biochem Mol Biol. 2008; 43(3): 189-219. One example of the fusion mechanisms is unifying Trimer-of-Hairpins Fusion Mechanism. Membrane fusion can occur after allosteric priming by binding to a target receptor. In some cases, membrane fusion occurs after proteolysis. In some cases, membrane fusion occurs after isomerization of disulfide bridges. In some cases, membrane fusion occurs by internalization and then priming of fusion via (i) cathepsin-mediated proteolysis, or (ii) low pH / acidification. The cathepsin-mediated proteolysis can be pH dependent or pH independent. Other fusion triggering mechanisms can include low PH, binding to target cell receptors, and a receptor followed by low pH. The envelope protein can also play a role in the formation of the lipid delivery particle. The envelope protein can interact with another component within the lipid delivery particle and participate in the assembly of the lipid delivery particle, for example, in a producer cell. The envelope protein can make contact with another envelope protein and form an oligomer embedded within the membrane. The envelope protein can be a glycoprotein, for example, a transmembrane glycoprotein. In some cases, envelope protein comprises multiple membrane -spanning regions. These multiple membranespanning regions can oligomerize and form channels in the membrane.

[0076] In some cases, the envelope protein is fused with a targeting moiety. In some cases, the targeting moiety recognizes a specific molecule (e.g., antigen, receptor, or other membrane protein) on the surface of a target cell to allow targeted cell entry with more specificity. In some cases, the targeting moiety is specific for a certain cell type or is specific for a certain target cell. The targeting moiety can be fused to the envelope protein at a position that is located at an outside of the lipid delivery particle. For example, the targeting moiety includes scFvs, antibody variable regions, nanobodies, T-cell receptor variable regions, other antigen-binding fragments or their mimetics, such as DARPins. In some cases, the targeting moiety is a protein ligand from the human ligandome. The targeting moiety can be a natural peptide or a synthetic peptide. In some cases, the targeting moiety is not fused with the envelope protein and is attached to the membrane of the lipid delivery particle from the outside, for example, via a transmembrane domain.

[0077] A targeting moiety can include, e.g. , an antibody or an antigen-binding fragment thereof (e.g. , Fab, Fab', F(ab')2, Fv fragments, scFv antibody fragments, disulfide-linked Fvs (sdFv), a Fd fragment consisting of the VH and CHI domains, linear antibodies, single domain antibodies such as sdAb (either VL or VH), nanobodies, or camelid VHH domains), an antigen-binding fibronectin type III (Fn3) scaffold such as a fibronectin polypeptide minibody, a ligand, a cytokine, a chemokine, or a T cell receptor (TCRs). Membrane -fusion proteins can be re-targeted by non-covalently conjugating a targeting moiety to the membrane-fusion protein or targeting protein (e.g. the hemagglutinin protein). For example, themembrane -fusion protein can be engineered to bind the Fc region of an antibody that targets an antigen on a target cell, redirecting the membrane fusion activity towards cells that display the antibody’s target.

[0078] In some cases, the targeting moiety linked to the membrane-fusion protein binds a cell surface marker on the target cell, e.g., a protein, glycoprotein, receptor, cell surface ligand, agonist, lipid, sugar, class I transmembrane protein, class II transmembrane protein, or class III transmembrane protein.

[0079] In some cases, the lipid delivery particles disclosed herein display targeting moieties that are not conjugated to the membrane-fusion protein or other proteins in order to redirect the fusion activity of the lipid delivery particle towards a cell that is bound by the targeting moiety, or to affect tropism of the lipid delivery particle toward the target cell.Envelope protein of viral origin

[0080] In some cases, an envelope protein has a viral origin. For example, a suitable envelope protein is from a DNA virus, an RNA virus, or a retrovirus. The envelope protein can be envelope protein from Herpesviruses, Avian sarcoma leukosis virus, Poxviruses, Hepadnaviruses, Asfarviridae, Flaviviruses, Alphaviruses, Togaviruses, Coronaviruses, Hepatitis D, Orthomyxoviruses, Rhabdovirus, Bunyaviruses, Filoviruses, Oncoretroviruses, lentiviruses, Spumaviruses. In some cases, envelope protein can be envelope protein from lentiviruses, for example, human immunodeficiency virus (HIV), simian immunodeficiency virus (SIV), feline immunodeficiency virus (FIV) and equine infectious anemia virus (EIAV). In some cases, an envelope protein is a fusion of two different envelope proteins, wherein each comes from a different virus. Additional suitable envelope proteins that are from viral origins and their functions are described in White JM et al., Crit Rev Biochem Mol Biol. 2008 May-Jun;43(3): 189-219.

[0081] In some cases, the envelope protein is a vesicular stomatitis virus glycoprotein (VSVG) or a biologically active mutant thereof. A “biologically active mutant” disclosed herein in connection with a reference protein can refer to a mutant of the reference protein that remains displaying one or more biological activities that are of same nature as the reference protein, which are relevant to the context in which the reference protein is used in the lipid delivery particle disclosed herein, while the level of the one or more biological activities of the biologically active mutant can be either similar as or different than the reference protein. For instance, the biologically active mutant of a VSVG in the context of an envelope protein remains displaying the biological activities of an envelope protein, e.g., mediating membrane fusion, tropism of the lipid delivery particle toward a target cell, or both. Unless otherwise noted, a mutant as described in the present disclosure is equivalent to a biologically active mutant. In some cases, the envelope protein is a Human immunodeficiency virus GP160 or a biologically active mutant thereof. In some cases, the envelope protein is a Baboon Endogenous Retrovirus (BaEVTR) glycoprotein or a biologically active mutant thereof. In some cases, the envelope protein is a modified Baboon Endogenous Retrovirus (BaEVTRless) glycoprotein or a biologically active mutant thereof. In some cases, the envelope protein is the fusion protein of Vesicular stomatitis Indiana virus and Rabies virus Glycoproteins (FuG-E) or a biologically active mutant thereof. In some cases, the envelope protein pantropic murine leukemia virus envelope protein (MLV) or a biologically active mutant thereof. In some cases, the envelope protein is a modified Fusion protein of Vesicular stomatitis Indiana virus and Rabiesvirus Glycoproteins (FuG-E P440E) or a biologically active mutant thereof. In some cases, the envelope protein is an ecotrophic Murine Leukemia Virus envelope protein (MLV ENV ecotropic) or a biologically active mutant thereof. In some cases, the envelope protein is an amphotrophic Murine Leukemia Virus envelope protein (MLV ENV amphotropic) or a biologically active mutant thereof. In some cases, the envelope protein is a Moloney murine leukemia virus envelope protein (MMLV) or a biologically active mutant thereof. In some cases, the envelope protein is a Moloney murine sarcoma virus envelope protein (MoMSVg) or a biologically active mutant thereof. In some cases, the envelope protein is a moloney murine leukemia virus 10A1 strain Glycoprotein (MLV 10A1) or a biologically active mutant thereof. In some cases, the envelope protein is a xenotropic murine leukemia virus envelope protein (MLV ENV xenotropic) or a biologically active mutant thereof. In some cases, the envelope protein is a xenotropic murine leukemia virus-related envelope protein (XMRV) or a biologically active mutant thereof. In some cases, the envelope protein is a Baculovirus envelope glycoprotein (GP64) or a biologically active mutant thereof. In some cases, the envelope protein is an endogenous feline virus envelope protein (RD114 ENV) or a biologically active mutant thereof. In some cases, the envelope protein is a mammalian endogenous retrovirus protein. The mammalian endogenous retrovirus protein can be a koala retrovirus protein (KoRV) or a Jaagsiekte sheep retrovirus protein (enJSRV), or a biologically active mutant thereof.

[0082] In some cases, the envelope protein is a simian endogenous type D retrovirus protein (RD-114) or a biologically active mutant thereof. In some cases, the envelope protein is a gibbon ape leukemia virus envelope protein (GALV) or a biologically active mutant thereof. In some cases, the envelope protein is a feline leukemia virus envelope protein (FLV) or a biologically active mutant thereof. In some cases, the envelope protein is a mouse mammary tumor virus envelope protein (MMTV) or a biologically active mutant thereof. In some cases, the envelope protein is an avian leukosis virus envelope protein or a biologically active mutant thereof. In some cases, the envelope protein is a rous sarcoma virus envelope protein or a biologically active mutant thereof.

[0083] In some cases, the envelope protein can direct the lipid delivery particles to fuse with a certain type of target cells rather than other cells. For example, based on the specific type of envelope protein associated with the membrane of the lipid delivery particle, the lipid delivery particle can preferentially target different cell types (z.e., tropisms of the lipid delivery particles), such as liver cells, ocular cells, nerve cells, lung cells, immune cells, muscle cells, and any other cell types of interest. For example, to fuse with a target liver cells, the envelope protein can be a glycoprotein from human hepatitis viruses or a biologically active mutant thereof, e.g., Hepatitis B virus (HBV) or hepatitis C virus (HCV), VSV-G glycoprotein or a mutant thereof, a Marburg virus glycoprotein or a biologically active mutant thereof, an Ebola virus glycoprotein or a mutant thereof. To fuse with a target muscle cell, for example, a skeletal muscle cell, the envelope protein can be a Ross River virus glycoprotein or a biologically active mutant thereof, or a VSV-G or a biologically active mutant thereof. To fuse with a target ocular cell, for example, a photoreceptor cell or a retinal cell, the envelope protein can be an Ebola virus glycoprotein or a biologically active mutant thereof, a Marburg virus glycoprotein or a mutant thereof, or a VSV-G or a biologically active mutant thereof. To fuse with a target immune cell, for example, CD8+ T cell, anHTLV-1 glycoprotein or a biologically active mutant thereof, or a VSV- G glycoprotein or a biologically active mutant thereof. To fuse with a target immune cell, for example, CD4+ T cell, the envelope protein can be a HIV-1 envelope or a biologically active mutant thereof, a HTLV-1 glycoprotein or a biologically active mutant thereof, or a VSV-G glycoprotein or a biologically active mutant thereof. To fuse with a target lung cells, the envelope protein can be a respiratory syncytial virus glycoprotein or a biologically active mutant thereof, or a SARS-CoV glycoprotein or a biologically active mutant thereof. To fuse with a target nerve cell, such as a cell from the central nervous system cell (e.g., neurons, glial cells including oligodendrocytes, astrocytes and microglia), the envelope protein can be a rabies glycoprotein or a biologically active mutant thereof, a Mokola virus glycoprotein or a mutant thereof, a Semliki Forest virus glycoprotein or a mutant thereof, a Venezuelan equine encephalitis virus glycoprotein or a mutant thereof, or a VSV-G or a biologically active mutant thereof. To fuse with a target sensory cell, such as an auditory cells, including hair cells, cochlear cells, etc., the envelope protein can be an Ebola virus glycoprotein or a biologically active mutant thereof, a Marburg virus glycoprotein or a biologically active mutant thereof, or a VSV-G or a biologically active mutant thereof.

[0084] In some cases, the envelope protein includes those described in Table 1 with at least one amino acid substitution, deletion, or insertion. For instance, N-terminal methionine can be absent from the envelope protein of the lipid delivery particle provided herein relative to the wild-type viral envelope protein. In some cases, the envelope protein includes those described in Table 1 and a heterologous peptide sequence fused to the N-terminal or C-terminal.

[0085] In some cases, the envelope protein comprises one or more of the sequences set forth in Table 1 with at least one amino acid substitution, deletion, or insertion. For instance, N-terminal methionine can be absent from the envelope protein of the lipid delivery particle provided herein relative to the wild-type viral envelope protein. In some cases, the envelope protein comprises one or more of the sequences set forth in Table 1 and a heterologous peptide sequence fused to the N-terminal or C-terminal.

[0086] In some cases, the envelope protein comprises any one of the sequences set forth in Table 1 with at least one amino acid substitution, deletion, or insertion. For instance, N-terminal methionine can be absent from the envelope protein of the lipid delivery particle provided herein relative to the wild-type viral envelope protein. In some cases, the envelope protein comprises any one of the sequences set forth in Table 1 and a heterologous peptide sequence fused to the N-terminal or C-terminal.

[0087] In some cases, the envelope protein comprises an amino acid sequence that has at least about 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence set forth in Table 1. In some cases, the envelope protein comprises an amino acid sequence that has at least about 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence set forth in any one of SEQ ID NOs: 83-104. In some cases, the envelope protein comprises an amino acid sequence that has at least about 50% sequence identity to a sequence set forth in any one of SEQ ID NOs: 83-104. In some cases, the envelope protein comprises an amino acid sequence that has at least about 60% sequence identity to a sequence set forth in any one of SEQ ID NOs: 83-104 In some cases, the envelope protein comprises an amino acid sequencethat has at least about 70% sequence identity to a sequence set forth in any one of SEQ ID NOs: 83-104. In some cases, the envelope protein comprises an amino acid sequence that has at least about 75% sequence identity to a sequence set forth in SEQ ID NOs: 83-104. In some cases, the envelope protein comprises an amino acid sequence that has at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence set forth in SEQ ID NOs: 83-104. In some cases, the envelope protein comprises an amino acid sequence that has at least about 80% sequence identity to a sequence set forth in SEQ ID NOs: 83-104. In some cases, the envelope protein comprises an amino acid sequence that has at least about 85% sequence identity to a sequence set forth in SEQ ID NOs: 83-104. In some cases, the envelope protein comprises an amino acid sequence that has at least about 90% sequence identity to a sequence set forth in SEQ ID NOs: 83-104 In some cases, the envelope protein comprises an amino acid sequence that has at least about 95% sequence identity to a sequence set forth in SEQ ID NOs: 83-104. In some cases, the envelope protein comprises an amino acid sequence that has at least about 96% sequence identity to a sequence set forth in SEQ ID NOs: 83-104. In some cases, the envelope protein comprises an amino acid sequence that has at least about 97% sequence identity to a sequence set forth in SEQ ID NOs: 83-104.In some cases, the envelope protein comprises an amino acid sequence that has at least about 98% sequence identity to a sequence set forth in SEQ ID NOs: 83-104. In some cases, the envelope protein comprises an amino acid sequence that has at least about 99% sequence identity to a sequence set forth in SEQ ID NOs: 83-104.Table 1. Exemplary envelope proteins from virus originEnvelope protein of human origin

[0088] In some aspects, the envelope protein in the lipid delivery particle described herein has a human origin, e.g., has significant sequence similarity to a human wild-type protein, such as at least 90%, at least 95%, at least 98%, or at least 99%. Using an envelope protein of a human origin can have benefits such as providing a minimized immunogenicity and better tolerance in a human subject receiving the lipid delivery particles. The lipid delivery particle comprising an envelope protein of a human origin can comprise another component that is from human origin or from non-human origin (e.g., a payload or a plasma membrane recruitment element). An envelope protein that is from human origin can include, example, envelope proteins or glycoproteins of human endogenous retroviruses (HERVs), other human endogenous envelope proteins, or other human endogenous proteins that serve a similar function of recognizing and / or fusing with membrane of a target cell (e.g., clathrin adaptor protein complex- 1, CHMP4C, Proteolipid protein 1, TSAP6, immunoglobulin variable domains, or a biologically active mutant thereof).

[0089] In some cases, the envelope protein is a HERV envelope protein such as any one of those listed in Table 2. In some cases, the envelope protein is a hENVHl or a biologically active thereof. In some cases, the envelope protein is a hENVH2 or a biologically active mutant thereof. In some cases, the envelope protein is a hENVH3 or a biologically active mutant thereof. In some cases, the envelope protein is a hENVKl or a biologically active mutant thereof. In some cases, the envelope protein is a hENVK2 or a biologically active mutant thereof. In some cases, the envelope protein is a hENVK3 or a biologically active mutant thereof. In some cases, the envelope protein is a hENVK4 or a biologically active mutant thereof. In some cases, the envelope protein is a hENVK5 or a biologically active mutant thereof. In some cases, the envelope protein is a hENVK6 or a biologically active mutant thereof. In some cases, the envelope protein is a hENVT or a biologically active mutant thereof. In some cases, the envelope protein is a hENVW or a biologically active mutant thereof. In some cases, the envelope protein is a hENVFRD or a biologically active mutant thereof. In some cases, the envelope protein is a hENVR or a biologically active mutant thereof. In some cases, the envelope protein is a hENVR(b) or a biologically active mutant thereof. In some cases, the envelope protein is a hENVR(c)2 or a biologically active mutant thereof. In some cases, the envelope protein is a hENVR(c) 1 or a biologically active mutant thereof. In some cases, the envelope protein is a hENVKcon or a biologically active mutant thereof. In some cases, the envelope protein is a biologically active truncated HERV protein.Table 2. Exemplary human HERV envelope proteins

[0090] For example, for those amino acid sequences start with a N-terminal methionine, the N-terminal methionine can be absent. In some cases, the envelope protein comprises the sequences set forth in Table 3 and a heterologous peptide sequence fused to the N-terminal or C-terminal.

[0091] In some cases, the envelope protein comprises one or more of the sequences set forth in Table 3 with at least one amino acid substitution, deletion, or insertion. For instance, N-terminal methionine can be absent from the envelope protein of the lipid delivery particle provided herein relative to the wild-type viral envelope protein. In some cases, the envelope protein comprises one or more of the sequences set forth in Table 3 and a heterologous peptide sequence fused to the N-terminal or C-terminal.

[0092] In some cases, the envelope protein comprises any one of the sequences set forth in Table 3 with at least one amino acid substitution, deletion, or insertion. For instance, N-terminal methionine can be absent from the envelope protein of the lipid delivery particle provided herein relative to the wild-type viral envelope protein. In some cases, the envelope protein comprises any one of the sequences set forth in Table 3 and a heterologous peptide sequence fused to the N-terminal or C-terminal.

[0093] In some cases, the envelope protein comprises an amino acid sequence that has at least about 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence set forth in SEQ ID NOs: 49-82. In some cases, the envelope protein comprises an amino acid sequence that has at least about 50% sequence identity to a sequence set forth in SEQ ID NOs: 49-82. In some cases, the envelope protein comprises an amino acid sequence that has at least about60% sequence identity to a sequence set forth in SEQ ID NOs: 49-82. In some cases, the envelope protein comprises an amino acid sequence that has at least about 70% sequence identity to a sequence set forth in SEQ ID NOs: 49-82. In some cases, the envelope protein comprises an amino acid sequence that has at least about 75% sequence identity to a sequence set forth in SEQ ID NOs: 49-82. In some cases, the envelope protein comprises an amino acid sequence that has at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence set forth in SEQ ID NOs: 49-82. In some cases, the envelope protein comprises an amino acid sequence that has at least about 80% sequence identity to a sequence set forth in SEQ ID NOs: 49-82. In some cases, the envelope protein comprises an amino acid sequence that has at least about 85% sequence identity to a sequence set forth in SEQ ID NOs: 49-82. In some cases, the envelope protein comprises an amino acid sequence that has at least about 90% sequence identity to a sequence set forth in SEQ ID NOs: 49-82. In some cases, the envelope protein comprises an amino acid sequence that has at least about 95% sequence identity to a sequence set forth in SEQ ID NOs: 49-82. In some cases, the envelope protein comprises an amino acid sequence that has at least about 96% sequence identity to a sequence set forth in SEQ ID NOs: 49-82. In some cases, the envelope protein comprises an amino acid sequence that has at least about 97% sequence identity to a sequence set forth in SEQ ID NOs: 49-82.In some cases, the envelope protein comprises an amino acid sequence that has at least about 98% sequence identity to a sequence set forth in SEQ ID NOs: 49-82. In some cases, the envelope protein comprises an amino acid sequence that has at least about 99% sequence identity to a sequence set forth in SEQ ID NOs: 49-82.Table 3. Exemplary sequences for human HERV envelope proteinsPLASMA MEMBRANE RECRUITMENT ELEMENT

[0094] In some aspects, the lipid delivery particle provided herein comprises a plasma membrane recruitment element. The lipid delivery particle disclosed herein can comprise a membrane. In some cases, the membrane encapsulates a payload. In some cases, the lipid delivery particle comprises a plasma membrane recruitment element, for example, inside the cavity of the lipid delivery particle. The plasma membrane recruitment element can localize itself to the membrane of the lipid delivery particles. The plasma membrane recruitment element can be utilized to recruit a component (e.g., a payload) to the membrane of the lipid delivery particles via forming a chimeric protein of the plasma membrane recruitment element and a component to be localized to the membrane or other mechanisms of attachment. In some cases, the membrane encapsulates a protein core. In some cases, at least a portion of the plasma membrane recruitment element forms the basic structure of the lipid delivery particle, such as a portion of the protein core inside the lipid delivery particle. In some cases, at least a portion of the plasma membrane recruitment element binds to the membrane of the lipid delivery particle from the inside.

[0095] The plasma membrane recruitment element can play a role in the assembly of the lipid delivery particle, such as packing various components (e.g., a payload) into the lipid delivery particles. The plasma membrane recruitment element can direct budding of the lipid delivery particles from a producer cell. Insome cases, expressing plasma membrane recruitment element alone or together with an envelope protein disclosed herein in a producer cell can lead to formation of the lipid delivery particle.

[0096] In some cases, the plasma membrane recruitment element has a viral origin. For instance, the plasma membrane recruitment element comprises a retroviral gag protein, e.g., a retroviral polyprotein that comprises one or more of a matrix (MA) polypeptide, an RNA-binding phosphoprotein polypeptide, a capsid (CA) polypeptide, or a nucleocapsid (NC) polypeptide. The plasma membrane recruitment element can comprise HIV gag or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a gag from murine leukemia virus (MLV) or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a gag from Moloney murine leukemia virus (MMLV) or a biologically active mutant thereof. In some cases, the plasma membrane recruitment element forms structural protein that forms the protein core of the lipid delivery particles described herein. The plasma membrane recruitment element can comprise Respiratory syncytial virus (RSV) M or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Human Papillomavirus (HPV) LI protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise HPV L2 protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Hepatitis B virus (HBV) core protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Hepatitis C virus (HCV) core protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise hepatitis E virus (HeV) M protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Chikungunya virus (CHIKV) C-E3-E2-6k-El or a biologically active mutant thereof. The plasma membrane recruitment element can comprise RSV NP or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Human metapneumovirus (HMPV) M or a biologically active mutant thereof. The plasma membrane can comprise a glycoprotein from a flavivirus. The flavivirus can comprise Chikungunya virus, Zika virus, Dengue virus, or West Niles virus. The plasma membrane recruitment element can comprise Zika virus (ZIKV) C or a biologically active mutant thereof. The plasma membrane recruitment element can comprise ZIKV prM / M or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Dengaue virus (DENV) C-prM or a biologically active mutant thereof. The plasma membrane recruitment element can comprise West Nile Virus (WNV) prME protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise WNV CprME protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Filovirus VP40 or Z protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Baculovirus P 1 protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Rotavirus VP7 or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Rotavirus VP2 protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Rotavirus VP6 protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Porcine Circovirus Type 2 (PCV2) capsid or a biologically active mutant thereof. The plasma membrane recruitment element cancomprise baculovirus VP2 protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise baculovirus VP5 protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise baculovirus VP3 protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise or baculovirus VP7 protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Ebola nucleocapsid or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Parovirus VP 1 protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Parovirus VP2 protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Newcastle disease virus (NDV) M protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Human polyomavirus 2 (JCPyV) VP1 protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise Human parainfluenza virus type 3 (HPIV3) M protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise HPIV3N protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise or Mumps virus (MuV) M proteins or a biologically active mutant thereof. The plasma membrane recruitment element can comprise SARS M protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise SARS E protein or a biologically active mutant thereof. The plasma membrane recruitment element can comprise SARS N protein or a biologically active mutant thereof.

[0097] In some cases, the plasma membrane recruitment element is a mammalian protein or part thereof. For example, the plasma membrane recruitment element can include a pleckstrin homology (PH) domain or a transmembrane domain of a mammalian protein, such as a mouse protein or a human protein. In some cases, the plasma membrane recruitment element has a human origin. Utilizing the plasma membrane recruitment element of a human origin in the lipid delivery particle can give rise to reduced immunogenicity for administration to a human subject. The plasma membrane recruitment element can include a gag from human endogenous retrovirus, such as Human Endogenous Retrovirus K (e.g., HERV- K113, HERV-K101, HERV-K102, HERV-K104, HERV-K107, HERV-K108, HERV-K109, HERV- K115, HERV- KI lp22, and HERV-K12ql3) and Human Endogenous Retrovirus-W (HERV-W) or a biologically active mutant thereof. The plasma membrane recruitment element can include a hGAGKcon or a biologically active mutant thereof. The plasma membrane recruitment element can include an endogenous gag of a mammal (e.g., human) from retrotransposons (e.g., Arc from vertebrate lineage of Ty3 / gypsy retrotransposon), which are also ancestral to retroviruses. In some cases, the plasma membrane recruitment element comprises a portion from human Arc.

[0098] The plasma membrane recruitment element can include a pleckstrin homology (PH) domain from a mammalian protein or a biologically active mutant thereof. The plasma membrane recruitment element can include a pleckstrin homology (PH) domain from a human protein or a biologically active mutant thereof. The PH domains can play a role in protein-membrane interactions via binding to phosphatidylinositol phosphate (PIP), for example PIP2 or PIP3, or other lipids or proteins within the membrane of the lipid delivery particles. PH domains with different sequences can have varied affinitiesand selectivity when binding different PIPs. The plasma membrane recruitment element can include a PH domain of phospholipase C51 (e.g., human phospholipase C51) or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a PH domain of Aktl (e.g., human Aktl) or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a mutant PH domain of human Aktl with E17K substitution or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a PH domain of 3 -phosphoinositide-dependent protein kinase 1 (e.g., human 3 -phosphoinositide-dependent protein kinase 1) or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a PH domain of Dappl (e.g., human Dappl) or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a PH domain of Grpl (e.g., mouse Grpl) or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a PH domain of human Grpl or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a PH domain of OSBP (e.g., human OSBP) or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a PH domain of Btkl (e.g., human Btkl) or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a PH domain of FAPP1 (e.g., human FAPP1) or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a PH domain of CERT (e.g., human CERT) or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a PH domain of PKD (e.g., human PKD) or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a PH domain of PHLPP1 (e.g., human PHLPP1) or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a PH domain of SWAP70 (e.g., human SWAP70) or a biologically active mutant thereof. The plasma membrane recruitment element can comprise a PH domain of MAPKAP1 (e.g., human MAPKAP1) or a biologically active mutant thereof.

[0099] The plasma membrane recruitment element can also include a membrane protein (e.g., a human membrane protein), a transmembrane domain thereof, or a biologically active mutant thereof. For example, the transmembrane domain of a human protein can be a tetraspanin or a biologically active mutant thereof. In some cases, the plasma membrane recruitment element comprises a transmembrane domain of human CD9 or a biologically active mutant thereof. In some cases, the plasma membrane recruitment element comprises a transmembrane domain of human CD47 or a biologically active mutant thereof. In some cases, the plasma membrane recruitment element comprises a transmembrane domain of human CD63 or a biologically active mutant thereof. In some cases, the plasma membrane recruitment element comprises a transmembrane domain of human CD81, or a biologically active mutant thereof.

[0100] The plasma membrane recruitment element can comprise a retroviral gag or a biologically active mutant thereof. The mutant of a retroviral gag can include only a portion of the retroviral gag. The plasma membrane recruitment element can include a gag of an alpha retrovirus or a biologically active mutant thereof. The plasma membrane recruitment element can a beta retrovirus or biologically active mutant thereof. The plasma membrane recruitment element can include a gamma retrovirus or biologically active mutant thereof. The plasma membrane recruitment element can include a delta retrovirus or biologicallyactive mutant thereof. The plasma membrane recruitment element can include or biologically active mutant thereof. The plasma membrane recruitment element can include an epsilon retrovirus or biologically active mutant thereof. The plasma membrane recruitment element can include a spumavirus or biologically active mutant thereof. The retroviral gag can include a gag of HIV (e.g., HIV-1), a gag of murine leukemia virus (MLV), a gag of Moloney murine leukemia virus (MMLV), a gag of Simian immunodeficiency virus (SIV), a gag of Rous sarcoma virus (RSV), a gag of human T-cell leukemia virus type-1 (HTLV), or a gag of bovine leukemia virus (BLV), or a biologically active mutant thereof. The plasma membrane recruitment element can include a gag of HIV (e.g., HIV-1) or a biologically active mutant thereof. The plasma membrane recruitment element can include a gag of MLV or a biologically active mutant thereof. The plasma membrane recruitment element can include a gag of RSV or a biologically active mutant thereof. The plasma membrane recruitment element can include a gag of Friend murine leukemia virus (FMLV) or biologically active mutant thereof.

[0101] In some cases, the plasma membrane recruitment element comprises one or more of the sequences set forth in Table 4 with at least one amino acid substitution, deletion, or insertion. For instance, N-terminal methionine can be absent from the plasma membrane recruitment element of the lipid delivery particle provided herein relative to the wild-type viral plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises one or more of the sequences set forth in Table 4 and a heterologous peptide sequence fused to the N-terminal or C-terminal.

[0102] In some cases, the plasma membrane recruitment element comprises any one of the sequences set forth in Table 4 with at least one amino acid substitution, deletion, or insertion. For instance, N-terminal methionine can be absent from the plasma membrane recruitment element of the lipid delivery particle provided herein relative to the wild-type viral plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises any one of the sequences set forth in Table 4 and a heterologous peptide sequence fused to the N-terminal or C-terminal.

[0103] In some cases, the plasma membrane recruitment element comprises the sequences set forth in Table 4 with a further truncation on the N-terminus. For example, for those amino acid sequences start with a N-terminal methionine, the N-terminal methionine can be absent. In some cases, the plasma membrane recruitment element comprises the sequences set forth in Table 4 with a further truncation on the C-terminus. In some cases, the plasma membrane recruitment element comprises the sequences set forth in Table 4 with one amino acid substitution. In some cases, the plasma membrane recruitment element comprises the sequences set forth in Table 4 with two or more amino acid substitutions. In some cases, the plasma membrane recruitment element comprises the sequences set forth in Table 4 and a heterologous peptide sequence fused to the N-terminal or C-terminal.

[0104] In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence set forth in Table 4. In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence setforth in any one of SEQ ID NOs: 1-48. In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 50% sequence identity to a sequence set forth in any one of SEQ ID NOs: 1-48. In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 60% sequence identity to a sequence set forth in any one of SEQ ID NOs: 1-48. In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 70% sequence identity to a sequence set forth in any one of SEQ ID NOs: 1-48. In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 75% sequence identity to a sequence set forth in any one of SEQ ID NOs: 1-48. In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence set forth in any one of SEQ ID NOs: 1-48. In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 80% sequence identity to a sequence set forth in any one of SEQ ID NOs: 1-48. In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 85% sequence identity to a sequence set forth in any one of SEQ ID NOs: 1-48. In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 90% sequence identity to a sequence set forth in any one of SEQ ID NOs: 1-48. In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 95% sequence identity to a sequence set forth in any one of SEQ ID NOs: 1-48. In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 96% sequence identity to a sequence set forth in any one of SEQ ID NOs: 1-48. In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 97% sequence identity to a sequence set forth in any one of SEQ ID NOs: 1-48. In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 98% sequence identity to a sequence set forth in any one of SEQ ID NOs: 1-48. In some cases, the plasma membrane recruitment element comprises an amino acid sequence that has at least about 99% sequence identity to a sequence set forth in any one of SEQ ID NOs: 1-48.Table 4. Exemplary plasma membrane recruitment elements and their sequences

[0105] *hGAGKcon is a consensus sequence from ten proviral GAG sequences. The GAG sequences used to derive this consensus GAG sequence are from the following HERVs: HERV-K113, HERV-K101, HERV-K102, HERV-K104, HERV-K107, HERV-K108, HERV-K109, HERV-K115, HERV- KI lp22, and HERV-K12ql3.

[0106] In some cases, the lipid delivery particle disclosed herein comprises a protein core that is composed of at least a structural protein of a viral origin, for instance, a retroviral gag protein. In some of these cases, the lipid delivery particle comprises a retroviral gag-pro-pol polyprotein, e.g., a gag-pro-pol poly protein from HIV, MMLV, or FMLV, which can help assemble a protein core of the lipid delivery particle. In some of these cases, some of the gag-pro-pol polyprotein is cleaved, e.g., by pro (protease) present freely or in the gag-pro-pol polyprotein. Without wishing to be bound by any particular theory, the cleavage by pro can be inefficient, and the resultant cleavage products can include gag polyprotein, gag -pro polyprotein, free pro, and free pol (polymerase). In some cases, a retroviral gag polyprotein can be further cleaved into MA, CA, NC, and other small fragments, if any. In some other cases, the lipid delivery particle comprises a retroviral gag-pro polyprotein without the pol component, and the gag-pro polyprotein can help form a protein core of the lipid delivery particle. The gag -pro can also be cleaved by pro, in some cases, inefficiently, into separate gag and pro proteins. In some cases, there can be different plasma membrane recruitment elements in a lipid delivery particle. For instance, a gag -pro or gag-pro-pol polyprotein from one species of virus (e.g., a retrovirus, e.g., a HIV) can help assemble form a protein core of the lipid delivery particle, while a chimeric protein in the lipid delivery particle, discussed infra, can comprise a payload fused with a gag protein from a different species of virus (e.g., an MMLV), orfrom a HERV, or a PH domain or transmembrane domain of a huma protein (e.g. , a PH domain of humanAktl with E17K substitutionMutant gag polyprotein

[0107] In some aspects, disclosed herein is a recombinant protein comprising a plasma membrane recruitment element comprising a mutant gag polyprotein. Also disclosed herein is a lipid delivery particle comprising a plasma membrane recruitment element comprising a mutant gag polyprotein. The mutant gag polyprotein is a mutant of a corresponding wild-type gag polyprotein. Relative to a wild-type gag polyprotein, a mutant gag polyprotein comprises an amino acid insertion, an amino acid deleteion, an amino acid substituion or any combinations thereof. In some cases, a mutant gag polyprotein comprises at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 40% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 45% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 50% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 55% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 60% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 65% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 70% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 75% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 80% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 85% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 90% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 91% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 92% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 93% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 94% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 95% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 96% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 97% identity to a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises at least about 98% identity to a corresponding wild-type gag polyprotein.

[0108] A wild-type gag polyprotein can comprise various domains, such as a matrix domain, an RNA- binding phosphoprotein, a capsid (including a major homology region), nucleocapsid, a particle buddingmotif (also termed as “budding domain” or “late domain”), a spacer peptide, a gag-endogenous protease cleavage sequence. A gag -endogenous protease cleavage sequence is the cleavage sequence homologous to a mutant gag polyprotein described herein, e.g., the gag -endogenous protease cleavage sequence is naturally present in the wild-type version of the mutant gag polyprotein. For example, a gag -endogenous protease cleavage sequence for MMLV gag includes MSKLLATW.

[0109] In some cases, the mutant gag polyprotein is a mutant of a wild-type gag polyprotein of a retrovirus. In some cases, the retrovirus is an endogenous retrovirus. In some cases, the mutant gag polyprotein is a mutant of a retroviral gag polyprotein. The mutant of a retroviral gag protein can include only a portion of the wild-type retroviral gag protein. In some cases, the wild type retroviral gag protein is endogenous. In some cases, the retroviral gag protein can comprise a retroviral nucleocapsid domain and / or a retroviral matrix domain. In some cases, the retroviral gag protein can be a gag homology protein. In some cases, the gag homology protein can be Arc protein (e.g, Arcl), Asprvl, a Sushi-Class protein, a SCAN protein, or a PNMA protein. In some cases, the gag homology protein can be ZCC18, ZCH12, PNM8B, PNM6A, PNMA6E_i2, PMA6F, PMAGE, PNMA1, PNMA2, PNM8A, PNMA3, PNMA4, PNMA5, PNMA6, PNMA7, PNMA1, M0AP1, or CCD 8. In some cases, the Gag-homology protein is an Arc protein, e.g., hARC or dARCl. In some cases, the Gag -homology protein can comprise ASPRV1. In some cases, the Gag-homology protein is PEG10, RTL3, RTL10, or RTL1. In some cases, the Gag Homology protein is a SCAN protein, for example, PGBD1. In some cases, the PEG10 Gag homology protein is PEG10_i6 or PEG10_i2. In some cases, the gag homology protein can be Arc protein (e.g, Arcl), Asprvl, PNMA1, PNMA3, PNMA4, PNMA5, PNMA6, PNMA7, PEG10, RTL1, MOAP1, or ZCCHC12.

[0110] The plasma membrane recruitment element can include a mutant of a wild-type gag of an alpha retrovirus. The plasma membrane recruitment element can include a mutant of a wild-type gag of a beta retrovirus. The plasma membrane recruitment element can include a mutant of a wild-type gag of a gamma retrovirus. The plasma membrane recruitment element can include a mutant of a wild-type gag of a delta retrovirus. The plasma membrane recruitment element can include a mutant of a wild-type gag of an epsilon retrovirus. The plasma membrane recruitment element can include a mutant of a wild-type gag of a spumavirus. The retroviral gag can include a mutant of a wild-type gag of HIV (e.g., HIV-1), a mutant of a wild-type gag of murine leukemia virus (MLV), a mutant of a wild-type gag of Moloney murine leukemia virus (MMLV), a mutant of a wild-type gag of Simian immunodeficiency virus (SIV), a mutant of a wild-type gag of Rous sarcoma virus (RSV), a mutant of a wild-type gag of human T-cell leukemia virus type-1 (HTLV), or a mutant of a wild-type gag of bovine leukemia virus (BLV). The plasma membrane recruitment element can include a mutant of a wild-type gag of HIV (e.g., HIV-1). The plasma membrane recruitment element can include a mutant of a wild-type gag of MLV. The plasma membrane recruitment element can include a mutant of a wild-type gag of MMLV. The plasma membrane recruitment element can include a mutant of a wild-type gag of RSV. The plasma membrane recruitment element can include a mutant of a wild-type gag of Friend murine leukemia virus (FMLV). The plasma membrane recruitment element can include a mutant of a wild-type gag of RousSarcoma Virus. The plasma membrane recruitment element can include a mutant of a wild-type gag of Avian Leukosis Virus. The plasma membrane recruitment element can include a mutant of a wild-type gag of Avian Myeloblastosis Virus. The plasma membrane recruitment element can include a mutant of a wild-type gag of Avian Myeloblastosis Virus. The plasma membrane recruitment element can include a mutant of a wild-type gag of Human T cell Leukemia V irus- 1. The plasma membrane recruitment element can include a mutant of a wild-type gag of Mouse Mammary Tumor Virus. The plasma membrane recruitment element can include a mutant of a wild-type gag of Jaagsiekte sheep retrovirus. The plasma membrane recruitment element can include a mutant of a wild-type gag of Mason-Pfizer Monkey Virus. In some cases, a wild-type gag polyprotein comprises an amino acid sequence selected from any one of sequence set forth in Table 15. In some cases, a wild-type gag polyprotein comprises an amino acid sequence selected from any one of SEQ ID Nos 285-298.[oni] In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to any one of sequence set forth in Table 15. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 50% sequence identity to any one of sequence set forth in Table 15. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 60% sequence identity to any one of sequence set forth in Table 15. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 70% sequence identity to any one of sequence set forth in Table 15. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 75% sequence identity to any one of sequence set forth in Table 15. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 75% sequence identity to any one of sequence set forth in Table 15. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 80% sequence identity to any one of sequence set forth in Table 15. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 85% sequence identity to any one of sequence set forth in Table 15. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 90% sequence identity to any one of sequence set forth in Table 15. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 95% sequence identity to any one of sequence set forth in Table 15. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 96% sequence identity to any one of sequence set forth in Table 15. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 97% sequence identity to any one of sequence set forth in Table 15. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 98% sequence identity to any one of sequence set forth in Table 15. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 99% sequence identity to any one of sequence set forth in Table 15.

[0112] In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to any one of sequence set forth in SEQ ID NO: 285-298. In some cases, the mutant gagpolyprotein comprises an amino acid sequence that has at least about 50% sequence identity to any one of sequence set forth in SEQ ID NO: 285-298. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 60% sequence identity to any one of sequence set forth in SEQ ID NO: 285-298. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 70% sequence identity to any one of sequence set forth in SEQ ID NO: 285-298. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 75% sequence identity to any one of sequence set forth in SEQ ID NO: 285-298. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 75% sequence identity to any one of sequence set forth in SEQ ID NO: 285-298. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 80% sequence identity to any one of sequence set forth in SEQ ID NO: 285-298. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 85% sequence identity to any one of sequence set forth in SEQ ID NO: 285-298. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 90% sequence identity to any one of sequence set forth in SEQ ID NO: 285-298. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 95% sequence identity to any one of sequence set forth in SEQ ID NO: 285-298. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 96% sequence identity to any one of sequence set forth in SEQ ID NO: 285-298. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 97% sequence identity to any one of sequence set forth in SEQ ID NO: 285-298. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 98% sequence identity to any one of sequence set forth in SEQ ID NO: 285-298. In some cases, the mutant gag polyprotein comprises an amino acid sequence that has at least about 99% sequence identity to any one of sequence set forth in SEQ ID NO: 285-298. In some cases, the mutant gag polyprotein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, or 99% of the entire amino acid sequence of the wild type gag polyprotein that comprises an amino acid sequence selected from Table 15. In some cases, the mutant gag polyprotein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, or 99% of the entire amino acid sequence of the wild type gag polyprotein that comprises an amino acid sequence set forth in any one of SEQ ID NO: 285-298. In some cases, the mutant gag polyprotein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, or 99% of the entire amino acid sequence of the wild type gag polyprotein that comprises an amino acid sequence selected from Table 15. In some cases, the mutant gag polyprotein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9 ,10, 20, 30, 40, 50, 60, 70, 80, 90, 100 or more mutations (e.g., amino acid deletions, insertion and / or substitutions) as compared to a wild-type polyprotein. In some cases, the mutant gagpolyprotein comprises a truncation (e.g., at the N-terminus and / or at the C-terminus) of at least about 1, 2, 2, 3, 4, 5, 6, 7, 8, 9 ,10, 20, 30, 40, 50, 60, 70, 80, 90, 100 or more contiguous amino acid residues as compared to the wild type polyprotein.

[0113] In some cases, the mutant gag polyprotein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9 ,10, 20, 30, 40, 50, 60, 70, 80, 90, 100 or more mutations (e.g., amino acid deletions, insertion and / or substitutions) as compared to a wild-type polyprotein that comprises an amino acid sequence selected from Table 15. In some cases, the mutant gag-polyprotein comprises a truncation (e.g., at the N-terminus and / or at the C- terminus) of at least about 1, 2, 2, 3, 4, 5, 6, 7, 8, 9 ,10, 20, 30, 40, 50, 60, 70, 80, 90, 100 or more contiguous amino acid residues as compared to the wild type polyprotein that comprises an amino acid sequence set forth in any one of SEQ ID NO: 285-298.

[0114] The plasma membrane recruitment element can comprise a mutant of HIV gag. The plasma membrane recruitment element can comprise a mutant of a gag from murine leukemia virus (MLV). The plasma membrane recruitment element can comprise a mutant of a gag from Moloney murine leukemia virus (MMLV).

[0115] The plasma membrane recruitment element can comprise a mutant of Respiratory syncytial virus (RSV) M. The plasma membrane recruitment element can comprise a mutant of Human Papillomavirus (HPV) LI protein. The plasma membrane recruitment element can comprise a mutant of HPV L2 protein. The plasma membrane recruitment element can comprise a mutant of Hepatitis B virus (HBV) core protein. The plasma membrane recruitment element can comprise a mutant of Hepatitis C virus (HCV) core protein. The plasma membrane recruitment element can comprise a mutant of hepatitis E virus (HeV) M protein. The plasma membrane recruitment element can comprise a mutant of Chikungunya virus (CHIKV) C-E3-E2-6k-El . The plasma membrane recruitment element can comprise a mutant of RSV NP. The plasma membrane recruitment element can comprise a mutant of Human metapneumovirus (HMPV) M. The plasma membrane recruitment element can comprise a mutant of Influenza Ml . The plasma membrane recruitment element can comprise a mutant of Zika virus (ZIKV) C. The plasma membrane recruitment element can comprise a mutant of ZIKV prM / M. The plasma membrane recruitment element can comprise a mutant of Dengaue virus (DENV) C-prM. The plasma membrane recruitment element can comprise a mutant of West Nile Virus (WNV) prME protein. The plasma membrane recruitment element can comprise a mutant of WNV CprME protein. The plasma membrane recruitment element can comprise a mutant of Filovirus VP40 or Z protein. The plasma membrane recruitment element can comprise a mutant of Baculovirus Pl protein. The plasma membrane recruitment element can comprise a mutant of Rotavirus VP7. The plasma membrane recruitment element can comprise a mutant of Rotavirus VP2 protein. The plasma membrane recruitment element can comprise a mutant of Rotavirus VP6 protein. The plasma membrane recruitment element can comprise a mutant of Porcine Circovirus Type 2 (PCV2) capsid. The plasma membrane recruitment element can comprise a mutant of baculovirus VP2 protein. The plasma membrane recruitment element can comprise a mutant of baculovirus VP5 protein. The plasma membrane recruitment element can comprise a mutant of baculovirus VP3 protein. The plasma membrane recruitment element can comprise a mutant of or baculovirus VP7 protein. The plasma membrane recruitment element can comprise a mutant of Ebola nucleocapsid. The plasma membrane recruitment element can comprise a mutant of Parovirus VP 1 protein. The plasma membrane recruitment element can comprise a mutant of Parovirus VP2 protein. Theplasma membrane recruitment element can comprise a mutant of Newcastle disease virus (NDV) M protein. The plasma membrane recruitment element can comprise a mutant of Nipah virus (NIV) M protein. The plasma membrane recruitment element can comprise a mutant of Human polyomavirus 2 (JCPyV) VP1 protein. The plasma membrane recruitment element can comprise a mutant of Human parainfluenza virus type 3 (HPIV3) M protein. The plasma membrane recruitment element can comprise a mutant of HPIV3N protein. The plasma membrane recruitment element can comprise a mutant of or Mumps virus (MuV) M proteins. The plasma membrane recruitment element can comprise a mutant of SARS M protein. The plasma membrane recruitment element can comprise a mutant of SARS E protein. The plasma membrane recruitment element can comprise a mutant of SARS N protein.

[0116] In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that lacks at least a fragment of a matrix protein as compared to a wild-type gag polyprotein. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that lacks at least a fragment of a RNA-binding phosphoprotein as compared to a wild-type gag polyprotein, for example, MMLV gag. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that lacks at least a fragment of at least a fragment of a capsid protein as compared to a wildtype gag polyprotein. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that lacks at least a fragment of a gag -endogenous protease cleavage sequence as compared to a wild-type gag polyprotein. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that lacks a gag -endogenous protease cleavage sequence as compared to a wildtype gag polyprotein. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that lacks at least a fragment of a gag -endogenous protease cleavage sequence as compared to a wild-type gag polyprotein. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that comprises a mutant gag -endogenous protease cleavage sequence as compared to a wild-type polyprotein. In some cases, the mutant gag-endogenous protease clevage sequence comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9 ,10, 20, 30, 40, 50, 60, 70 , 80, 90 , 100 or more mutations (e.g. amino acid deletions, insertion and / or substitutions) as compared to a wild-type polyprotein. In some cases, the mutant gag-endogenous protease clevage sequence comprises a truncation (e.g., at the N- terminus and / or at the C-terminus) of at least about 1, 2, 2, 3, 4, 5, 6, 7, 8, 9 ,10, 20, 30, 40, 50, 60, 70 , 80, 90 , 100 or more contiguous amino acid residues as compared to a wild type polyprotein. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that comprises a mutant gag-endogenous protease cleavage sequence as compared to a wild-type polyprotein, wherein the mutant gag-endogenous protease cleavage sequence cannot be recognized or cleaved by the gag- endogenous protease. In some cases, the mutant gag -endogenous protease cleavage sequence is recognized or cleaved by a different protease than the gag -endogenous protease that recognizes the corresponding wild type gag-endogenous protease cleavage sequence. In some cases, the mutant gag- endogenous protease cleavage sequence exhibits improved clevage (higher cleavage efficiency) relative to that by corresponding wild type gag -endogenous protease cleavage sequence. In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that comprises (e.g., at leastone, 2, 3, 4, 5 or more) exogenous protease cleavage sequences as compared to a wild-type polyprotein. In some cases, an exogenous protease cleavage sequence is a protease cleavage sequence that does not naturally occur in the corresponding wild type polyprotein sequence. In some cases, an exogenous protease cleavage sequence links one or more domains of the mutant gag polyprotein.

[0117] In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein that lacks at least a fragment of a nucleocapsid protein as compared to a wild-type gag polyprotein.

[0118] In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein, for example, a mutant of wild-type HIV gag, a mutant of wild-type MMLV gag, a mutant of wild-type RSV gag, and a mutant of wild-type HERV gag.

[0119] In some cases, the plasma membrane recruitment element comprises a full-length capsid protein (i.e., the capsid protein of the wild-type gag). In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein comprising a fragment of a capsid protein of a corresponding wildtype gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 20% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 25% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 30% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 35% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 40% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 45% identity to the capsid protein of a corresponding wildtype gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 50% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 55% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 60% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 65% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 70% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 75% identity to the capsid protein of a corresponding wildtype gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 80% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 85% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, amutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 90% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 91% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 92% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 93% identity to the capsid protein of a corresponding wildtype gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 94% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 95% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 96% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 97% identity to the capsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a capsid protein comprising at least about 98% identity to the capsid protein of a corresponding wild-type gag polyprotein.

[0120] In some cases, the plasma membrane recruitment element comprises a full-length matrix protein (i.e., the matrix protein of the wild-type gag). In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein comprising a fragment of a matrix protein of a corresponding wildtype gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 20% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 25% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 30% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 35% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 40% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 45% identity to the matrix protein of a corresponding wildtype gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 50% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 55% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 60% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 65% identity to the matrixprotein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 70% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 75% identity to the matrix protein of a corresponding wildtype gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 80% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 85% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 90% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 91% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 92% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 93% identity to the matrix protein of a corresponding wildtype gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 94% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 95% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 96% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 97% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a matrix protein comprising at least about 98% identity to the matrix protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein lacks the matrix protein of a corresponding wild-type gag polyprotein.

[0121] In some cases, the plasma membrane recruitment element comprises a full-length nucleocapsid protein (i.e., the nucleocapsid protein of the wild-type gag). In some cases, the plasma membrane recruitment element comprises a mutant gag polyprotein comprising a fragment of a nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 20% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 25% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 30% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 35% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragmentof a nucleocapsid protein comprising at least about 40% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 45% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 50% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 55% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 60% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 65% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 70% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 75% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 80% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 85% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 90% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 91% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 92% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 93% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 94% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 95% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 96% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 97% identity to the nucleocapsid protein of a corresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein comprises a fragment of a nucleocapsid protein comprising at least about 98% identity to the nucleocapsid protein of acorresponding wild-type gag polyprotein. In some cases, a mutant gag polyprotein lacks the nucleocapsid protein of a corresponding wild-type gag polyprotein.

[0122] In some cases, the plasma membrane recruitment element comprises heterologous sequence. In some cases, the heterologous sequence is fused to a fragment of the matrix protein, such as the N-terminal of the fragment of the matrix protein. In some cases, the heterologous sequence is fused to a fragment of the capsid protein, such as the N-terminal of the fragment of the capsid protein. In some cases, the heterologous sequence is fused to a matrix protein or a fragment thereof. In some cases, the heterologous sequence is fused to a nucleocapsid protein or a fragment thereof. In some cases, the heterologous sequence is fused to a particle budding motif or a fragment thereof (e.g., a late domain of RSV). In some cases, the heterologous sequence is a pleckstrin homology (PH) domain or a mutant thereof, such as those listed in Table 4. In some cases, the PH domain is a human PH domain. In some cases, the fragment of the matrix protein lacks a N-terminal myristoylation motif, a N-terminal glycine, a highly basic region (HBR), a N-terminal fragment, or any combinations thereof. In some cases, the plasma membrane recruitment element comprises at least a portion of a nucleocapsid protein. In some cases, the plasma membrane recruitment element comprises two or more particle budding motifs described herein. In some cases, at least one of the two or more particle budding motifs is endogenous. In some cases, at least one of the two or more particle budding motifs is heterologous, such as RSV P2B or a mutant thereof. In some cases, at least one of the two or more particle budding motifs comprises a PTAP motif, a PPPY motif, a PPXY motif, a YXXL motif, a YPXnL motif, or any combinations thereof, and wherein n is an integer from 1 to 5. In some cases, at least one of the two or more particle budding motifs comprises a sequence listed in Table 5. In some cases, the plasma membrane recruitment element comprises comprises the mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of HIV and comprises at least a portion of a P6 domain. In some cases, the plasma membrane recruitment element comprises at least a N- terminal fragment of the P6 domain. In some cases, the plasma membrane recruitment element comprises at least a C-terminal fragment of the P6 domain. In some cases, the plasma membrane recruitment element comprises two spacer peptides (e.g., P2 domain, Pl domain, or both). In some cases, the plasma membrane recruitment element is fused to the post-translational modification motif as described herein. In some cases, the post-translational modification motif is fused to the N-terminus of the plasma membrane recruitment element. In some cases, the post-translational modification motif is fused to the C- terminus of the plasma membrane recruitment element. In some cases, the post-translational modification motif is a myristoylation motif. In some cases, the post-translational modification motif is an acetylation motif. In some cases, the post-translational modification motif is an isoprenylation motif. In some cases, the post-translational modification motif is a palmitoylation motif. In some cases, the post-translational modification motif is a famesylation motif. In some cases, the plasma membrane recruitment element is fused to the membrane penetrating peptide. In some cases, the membrane penetrating peptide is linked to the plasma membrane recruitment element. In some cases, the membrane penetrating peptide connects the plasma membrane recruitment element and a payload. In some cases, the membrane penetrating peptide comprises a sequence having at least about 80% sequence identity to a sequence listed in Table 6.

[0123] In some cases, the plamamembrane recruitment element comprises a mutant gag polyprotein of a wild-type Rous Sarcoma Virus (RSV) gag polyprotein. In some cases, the plamamembrane recruitment element lacks a capsid protein of the RSV gag. In some cases, the plamamembrane recruitment element lacks a nucleocapsid protein of the RSV gag. In some cases, the plamamembrane recruitment element comprises at least a portion of the matrix protein of the RSV gag. In some cases, the plasma membrane recruitment element comprises a matrix protein of the RSV gag and a late domain of the RSV gag. In some cases, the plasma membrane recruitment element comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a full-length nucleocapsid protein of the RSV. In some cases, the plasma membrane recruitment element comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a full-length nucleocapsid protein of the RSV arranged in order from N-terminus to C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a fragment of the nucleocapsid protein of the RSV gag. In some cases, the plasma membrane recruitment element comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a fragment of the nucleocapsid protein of the RSV gag arranged in order from N-terminus to C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element further comprises a N-terminal myristoylation motif. In some cases, the plasma membrane recruitment element comprises a matrix protein of the RSV gag and a late domain of the RSV gag arranged in order from N- terminus to C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element consists of a matrix protein of the RSV gag and a late domain of the RSV gag arranged in order from N-terminus to C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a fragment of a full-length nucleocapsid of the RSV gag arranged in order from N-terminus to C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element consists of a matrix protein of the RSV gag, a late domain of the RSV gag, and a fragment of a full-length nucleocapsid of the RSV gag arranged in order from N-terminus to C- terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a fragment of a full-length nucleocapsid of the RSV gag arranged in order from N-terminus to C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element consists of a myr group of the RSV gag, a late domain of the RSV gag, and a fragment of a full-length nucleocapsid of the RSV gag arranged in order from N-terminus to C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises a myr group of the RSV gag, a late domain of the RSV gag, and a fragment of a full-length nucleocapsid of the RSV gag arranged in order from N-terminus to C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element consists of a myr group of the RSV gag, a late domain of the RSV gag, and a full-length nucleocapsid of the RSV gag arranged in order from N-terminus to C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment elementcomprises a myr group of the RSV gag, a late domain of the RSV gag, and a full-length nucleocapsid of the RSV gag arranged in order from N-terminus to C-terminus of the plasma membrane recruitment element.In some cases, a plasma membrane recruitment element is linked to a payload (e.g., a base editor), for example, via a cleavable linker, which forms a chimeric protein descried herein. In some cases, a plasma membrane recruitment element is linked to a protease, for example, with or without a cleavable linker. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) includes any one of those described in Table 10A or Table 10B with at least one amino acid substitution, deletion, or insertion. For example, forthose amino acid sequences start with a N-terminal methionine, the N-terminal methionine can be absent. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) includes any one of those described in Table 10A or Table 10B and a heterologous peptide sequence (e.g., post-translational modification motif) fused to the N-terminal or C-terminal. The payload in some of the exemplary sequences in Table 10A and Table 10B can be replaced with any desired therapeutic molecule (e.g., a prime editor, an antibody, etc).

[0124] In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any one of sequence set forth in Table 10A or Table 10B. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 50% sequence identity to any one of sequence set forth in Table 10A or Table 10B. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 60% sequence identity to any one of sequence set forth in Table 10A or Table 10B. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 70% sequence identity to any one of sequence set forth in Table 10A or Table 10B. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 75% sequence identity to any one of sequence set forth in Table 10A or Table 10B. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any one of sequence set forth in Table 10A or Table 10B. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 80% sequence identity to any one of sequence set forth in Table 10A or Table 10B. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 85% sequence identity to any one of sequence set forth in Table 10A or Table 10B. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 90% sequence identity to any one of sequence set forth in Table 10A or Table 10B. In some cases, the plasma membrane recruitment elementwith or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 95% sequence identity to any one of sequence set forth in Table 10A or Table 10B. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 96% sequence identity to any one of sequence set forth in Table 10A or Table 10B. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 97% sequence identity to any one of sequence set forth in Table 10A or Table 10B. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 98% sequence identity to any one of sequence set forth in Table 10A or Table 10B. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 99% sequence identity to any one of sequence set forth in Table 10A or Table 10B. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any one of sequence set forth Table 10A. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any one of sequence set forth Table 10B. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence set forth in any one of SEQ ID NOs: 194-233. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence set forth in any one of SEQ ID NOs: 234-263. In some cases, the plasma membrane recruitment element with or without a payload (e.g., a base editor) comprises an amino acid sequence that has at least about 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence set forth in any one of SEQ ID NOs: 194-263Table 15 Exemplary wild type gag polyprotein and the corresponding amino acid sequencesMutant of an HIV Gag polyprotein

[0125] In some cases, the lipid delivery particle comprises a plasma membrane recruitment element comprising a mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of HIV, such as HIV- 1. In some cases, the plasma membrane recruitment element is fused to the cleavable linker. In some cases, the plasma membrane recruitment element is fused to the membrane penetrating peptide. In some cases, the plasma membrane recruitment element is fused to the post-translational modification motif. In some cases, the lipid delivery particle further comprises the envelope protein, and wherein the envelope protein comprises the envelope protein from human endogenous retrovirus (HERV) or a mutant thereof. Functions of various domains of HIV- 1 gag are described in Accola MA et al., J Virol. 2000 Jun;74(12): 5395-402 and Montagna C et al., Mol Ther Nucleic Acids. 2018 Sep 7; 12:453-462., each of which are incorporated herein by reference in its entirety.

[0126] In some cases, the plasma membrane recruitment element comprises at least a fragment of matrix protein of an HIV gag, such as a N-terminal fragment of the matrix protein of the HIV gag and a pleckstrin homology (PH) domain (e.g., a human PH domain or those listed in Table 4) or a mutant thereof. In some cases, the plasma membrane recruitment element comprises at least a fragment of capsid protein of the HIV gag, such as a full-length capsid protein of the HIV gag and a C-terminal fragment of capsid protein of the HIV gag. In some cases, the plasma membrane recruitment element comprises a spacer peptide of the HIV gag, such as a P2 domain of the HIV gag and a Pl domain of the HIV gag, or both.

[0127] In some cases, the plasma membrane recruitment element comprises a heterologous domain. In some cases, the heterologous domain can perform protein-protein interactions. In some cases, the heterologous domain comprises a multimerization motif. In some cases, the multimerization motif formsparallel homodimers, such as a coiled-coil. In some cases, the multimerization motif forms parallel heterodimers (e.g., dDZFl and dDZF2). In some cases, the multimerization motif forms dimers, trimers, tetramers, or other oligomers. In some cases, the coiled-coil is a leucine zipper (LZ), such as a GCN4 leucine zipper or a mutant thereof. In some cases, the plasma membrane recruitment element comprises a leucine zipper and lacks nucleocapsid protein of the HIV gag. In some cases, the plasma membrane recruitment element comprises a full-length nucleocapsid protein of the HIV gag or a fragment thereof.

[0128] In some cases, the plasma membrane recruitment element comprises a particle budding motif. In some cases, the plasma membrane recruitment element comprises two or more particle budding motifs. In some cases, the plasma membrane recruitment element comprises one, two, or three particle budding motifs. In some cases, at least one of the particle budding motifs is a particle budding motif of the HIV gag, for example, a N-terminal fragment of the P6 domain of the HIV gag, a PTAP motif, or a full-length P6 domain of the HIV gag. In some cases, at least one of the particle budding motifs is a heterologous particle budding motif, for example, RSV P2B or a mutant thereof or a sequence listed in Table 5.

[0129] In some cases, the plasma membrane recruitment element lacks at least a C-terminal fragment of matrix protein of the HIV gag. In some cases, the plasma membrane recruitment element lacks at least a spacer peptide of the HIV gag. In some cases, the plasma membrane recruitment element lacks at least a fragment of the P6 domain of the HIV gag. In some cases, the plasma membrane recruitment element lacks at least a fragment of the P6 domain of the HIV gag. In some cases, the plasma membrane recruitment element lacks at least a fragment of capsid protein of the HIV gag, such as lacking a N- terminal fragment or a C-terminal fragment. In some cases, the plasma membrane recruitment element lacks at least a fragment or all of the nucleocapsid protein of the HIV gag. In some cases, the plasma membrane recruitment element lacks a Pl domain domain of the HIV gag. In some cases, the plasma membrane recruitment element lacks a P2 domain domain of the HIV. In some cases, the plasma membrane recruitment element lacks a Pl domain and a P2 domain domain of the HIV gag. In some cases, the plasma membrane recruitment element lacks a C-terminal fragment of the HIV gag and a fragment of the capsid protein of the HIV gag. In some cases, the plasma membrane recruitment element lacks a C-terminal fragment of the HIV gag, a fragment of the capsid protein of the HIV gag, and at least a fragment of the nucleocapsid protein of the HIV gag. In some cases, the plasma membrane recruitment element lacks a C-terminal fragment of the HIV gag, a fragment of the capsid protein of the HIV gag, at least a fragment of the nucleocapsid protein of the HIV gag, and a Pl domain domain of the HIV gag. In some cases, the plasma membrane recruitment element lacks a C-terminal fragment of the HIV gag, a fragment of the capsid protein of the HIV gag, at least a fragment of the nucleocapsid protein of the HIV gag, and a P2 domain domain of the HIV gag. In some cases, the plasma membrane recruitment element lacks a C-terminal fragment of the HIV gag, a fragment of the capsid protein of the HIV gag, at least a fragment of the nucleocapsid protein of the HIV gag, a P 1 domain and a P2 domain domain of the HIV gag. In some cases, the plasma membrane recruitment element further lacks a HIV gag endogenous protease cleavage sequence or comprises a mutant HIV gag endogenous protease cleavage sequence that cannot be cleaved by a HIV protease.

[0130] In some cases, the plasma membrane recruitment element lacks a matrix protein of the HIV gag. In some cases, the plasma membrane recruitment element lacks a nucleocapsid protein of the HIV gag. In some cases, the plasma membrane recruitment element lacks a P6 domain of the HIV gag. In some cases, the plasma membrane recruitment element lacks a matrix protein of the HIV gag and a nucleocapsid protein of the HIV gag. In some cases, the plasma membrane recruitment element lacks a P2 domain of the HIV gag, a Pl domain of the HIV gag, or both. In some cases, the plasma membrane recruitment element lacks a matrix protein of the HIV gag, a P2 domain of the HIV gag, a nucleocapsid protein of the HIV gag, a Pl domain of the HIV gag, and a P6 domain of the HIV gag. In some cases, the plasma membrane recruitment element comprises a N-terminal N-terminal myristoylation motif, the full-length capsid protein of the HIV gag or a fragment thereof, the multimerization motif (optionally a DZF), and a heterologous particle budding motif (optionally a late domain of RSV) arranged in order from aN- terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises a N-terminal myristoylation motif of the HIV gag, the full-length capsid protein of the HIV gag or a fragment thereof, a dDZFl, and a late domain of RSV) arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element comprises a N-terminal myristoylation motif of the HIV gag, the full-length capsid protein of the HIV gag or a fragment thereof, a dDZF2, and a late domain of RSV) arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

[0131] In some cases, the plasma membrane recruitment element comprises(a) the N-terminal fragment of the matrix protein of the HIV gag or the pleckstrin homology (PH) domain or a mutant thereof;(b) the full-length capsid protein of the HIV gag or a fragment thereof;(c) the multimerization motif (e.g., leucine zipper) or the full-length nucleocapsid protein of the HIV gag or a fragment thereof; and(d) the particle budding motif.In some cases, the (a)-(d) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element further comprises the P2 domain of the HIV gag located at a position between (b) and (c).

[0132] In some cases, the plasma membrane recruitment element comprises the following configurations arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment:1) the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, P 1 domain of the HIV gag, and P6 domain of the HIV gag;) the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag. ) the N-terminal fragment of the matrix protein of the HIV gag, a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag. ) the N-terminal fragment of the matrix protein of the HIV gag, a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and P6 domain of the HIV gag; 0) the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, P 1 domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); 1) the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); 2) the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); 3) the N-terminal fragment of the matrix protein of the HIV gag, a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIVgag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5). ) the N-terminal fragment of the matrix protein of the HIV gag, a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5). ) the N-terminal fragment of the matrix protein of the HIV gag, a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag. ) the N-terminal fragment of the matrix protein of the HIV gag, a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag;) the N-terminal fragment of the matrix protein of the HIV gag, a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag. ) the N-terminal fragment of the matrix protein of the HIV gag, a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5);) the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5);) the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5);) the N-terminal fragment of the matrix protein of the HIV gag, a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5). ) the N-terminal fragment of the matrix protein of the HIV gag, a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5). ) the N-terminal fragment of the matrix protein of the HIV gag, a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5);) the N-terminal fragment of the matrix protein of the HIV gag, a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, P 1 domain of the HIV gag, and P6 domain of the HIV gag. ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, P 1 domain of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag. ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N-terminal fragment of capsid protein of theHIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, P 1 domain of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5).) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, P 1 domain of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5);) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5). ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5);) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5);) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag. ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag. ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N-terminal fragment of capsid protein of theHIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and P6 domain of the HIV gag; ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and a second particle budding domain (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5). ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5). ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and a second particle budding domain (e.g., a sequence selected from Table 5);) the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and a second particle budding domain (e.g., a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag;) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag.) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag;) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag.) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag;) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5);) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5). ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5). ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag;) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag. ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag. ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and P6 domain of the HIV gag; 0) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); 1) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); 2) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); 3) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5).) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5). ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag.) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C-terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag;) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag.) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and P6 domain of the HIV gag;) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), C- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a heterologous particle budding domain (e.g., RSV P2B or a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5).) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5). ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, Pl domain of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), C- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), Pl domain of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and P6 domain of the HIV gag;) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag. ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag. ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), C- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and P6 domain of the HIV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), the full-length capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif(e.g., leucine zipper), and a second particle budding domain (e.g., a sequence selected from Table 5);139) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5).140) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, full-length nucleocapsid protein of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5);141) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5).142) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a C- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a fragment of nucleocapsid protein of the HIV gag, and a second particle budding domain (e.g., a sequence selected from Table 5);143) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), a N- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and a second particle budding domain (e.g., a sequence selected from Table 5);144) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a first particle budding motif (e.g., RSV P2B or a sequence selected from Table 5), C- terminal fragment of capsid protein of the HIV gag, P2 domain of the HIV gag, a multimerization motif (e.g., leucine zipper), and a second particle budding domain (e.g., a sequence selected from Table 5);145) an HIV Gag myristoylation motif, a full-length capsid protein of the HIV gag or a fragment thereof, dDZFl, a particle budding domain (e.g., RSV late domains);146) an HIV Gag myristoylation motif, a full-length capsid protein of the HIV gag or a fragment thereof, dDZF2, a particle budding domain (e.g., RSV late domains);

[0133] In some cases, each of the configurations 1) to 144) listed in the preceding paragraph independently lacks a HIV gag endogenous protease cleavage sequence. In some cases, each of theconfigurations 1) to 144) listed above independently comprises a mutant HIV gag endogenous protease cleavage sequence that cannot be recognized and cleaved by an HIV protease. In some cases, in any one of configurations 1) to 144) listed above, the C-terminal fragment of capsid protein of the HIV gag comprises the major homology region (MHR). In some cases, each of the configurations 1) to 144) listed above is fused to a membrane penetrating peptide (e.g, a sequence selected from Table 6). In some cases, each of the configurations 1) to 144) listed above is fused to a post-translational modification motif on the N-terminus or the C-terminus (e.g., a sequence selected from Table 7). In some cases, the plasma membrane recruitment element comprises one, two, or three particle budding motif, each of which is selected from a sequence listed in Table 5. In some cases, in any one of the configurations 1) to 72) listed above, a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4) is fused the N-terminal of the fragment of the matrix protein, wherein the fragment of the matrix protein (a) lacks a N-terminal myristoylation motif, a N-terminal glycine, a highly basic region (HBR), a N-terminal fragment, or any combinations thereof or (b) comprises a mutated myr receptor by the amino acid substitution G2A on the matrix protein. In some cases, the plasma membrane recruitment element consists essentially of the domains in each of the configurations 1) to 144) listed in the preceding paragraph. In some cases, the plasma membrane recruitment element consists of the domains in each of the configurations 1) to 144) listed in the preceding paragraph.Mutant of an MLV Gag polyprotein

[0134] In some cases, the lipid delivery particle comprises a plasma membrane recruitment element comprising a mutant gag polyprotein that is not from HIV. In some cases, the mutant gag polyprotein is a mutant of a wild-type gag polyprotein of MMLV. In some cases, the plasma membrane recruitment element is fused to the cleavable linker. In some cases, the plasma membrane recruitment element is fused to the membrane penetrating peptide. In some cases, the plasma membrane recruitment element is fused to the post-translational modification motif. In some cases, the lipid delivery particle further comprises the envelope protein, and wherein the envelope protein comprises the envelope protein from human endogenous retrovirus (HERV) or a mutant thereof.

[0135] In some cases, the plasma membrane recruitment element comprises at least a fragment of matrix protein of an MMLV gag, such as a N-terminal fragment of the matrix protein of the MMLV gag and a pleckstrin homology (PH) domain (e.g., a human PH domain or those listed in Table 4) or a mutant thereof. In some cases, the plasma membrane recruitment element comprises at least a fragment of capsid protein of the MMLV gag, such as a full-length capsid protein of the MMLV gag and a C-terminal fragment of capsid protein of the MMLV gag. In some cases, the plasma membrane recruitment element comprises P12 domain of the MMLV gag or a fragment thereof. In some cases, a fragment of the P12 domain of the MMLV gag is fused to a particle budding motif (e.g., a sequence selected from Table 5). In some cases, the plasma membrane recruitment element lacks at least a C-terminal fragment of matrix protein of the MMLV gag. In some cases, the plasma membrane recruitment element lacks at least a fragment of the P 12 domain of the MMLV gag. In some cases, the plasma membrane recruitment elementlacks at least a fragment of the P 12 domain of the MMLV gag. In some cases, the plasma membrane recruitment element lacks at least a fragment of capsid protein of the MMLV gag, such as lacking a N- terminal fragment or a C-terminal fragment. In some cases, the plasma membrane recruitment element lacks at least a fragment or all of the nucleocapsid protein of the MMLV gag. In some cases, the plasma membrane recruitment element lacks a C-terminal fragment of the MMLV gag and a fragment of the capsid protein of the MMLV gag. In some cases, the plasma membrane recruitment element lacks a C- terminal fragment of the MMLV gag, a fragment of the capsid protein of the MMLV gag, and at least a fragment of the nucleocapsid protein of the MMLV gag. In some cases, the plasma membrane recruitment element further lacks a MMLV gag endogenous protease cleavage sequence or comprises a mutant MMLV gag endogenous protease cleavage sequence that cannot be cleaved by a MMLV protease.

[0136] In some cases, the plasma membrane recruitment element comprises a heterologous domain. In some cases, the heterologous domain comprises a multimerization motif. In some cases, the multimerization motif forms parallel homodimers, such as a coiled-coil. In some cases, the multimerization motif forms parallel heterodimers (e.g., dDZFl and dDZF2). In some cases, the multimerization motif forms dimers, trimers, tetramers, or other oligomers. In some cases, the coiled-coil is a leucine zipper (LZ), such as a GCN4 leucine zipper or a mutant thereof. In some cases, the plasma membrane recruitment element comprises a leucine zipper and lacks nucleocapsid protein of the MMLV gag. In some cases, the plasma membrane recruitment element comprises a full-length nucleocapsid protein of the MMLV gag or a fragment thereof.

[0137] In some cases, the plasma membrane recruitment element comprises a particle budding motif. In some cases, the plasma membrane recruitment element comprises two or more particle budding motifs. In some cases, the plasma membrane recruitment element comprises one, two, or three particle budding motifs. In some cases, at least one of the particle budding motifs is a particle budding motif of the MMLV gag, for example, a N-terminal fragment of the P12 domain of the MMLV gag, a PSAP motif, a LYPAL motif, a PPPY motif, or a full-length P12 domain of the MMLV gag. In some cases, at least one of the particle budding motifs is a heterologous particle budding motif, for example, RSV P2B or a mutant thereof or a sequence listed in Table 5.

[0138] In some cases, the plasma membrane recruitment element comprises(a) a matrix protein of the MMLV gag (optionally full-length matrix protein of the MMLV gag, a N-terminal fragment or a C-terminal fragment of the full-length matrix protein of the MMLV gag), a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof;(b) a capsid protein of the MMLV gag or a mutant thereof, optionally wherein the capsid protein of the MMLV gag or a mutant thereof is a full-length capsid protein of the MMLV gag, or a N- terminal fragment of or a C-terminal fragment of the full-length capsid protein of the MMLV gag;(c) heterologous domain, optionally wherein the heterologous domain comprises a coiled-coil (optionally a leucine zipper); and(d) an optional particle budding motif, optionally wherein the particle budding motif is particle budding motif of the MMLV gag; optionally wherein the particle budding motif is a heterologous particle budding motif; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof or a sequence listed in Table 5.

[0139] In some cases, the (a)-(d) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element. In some cases, the plasma membrane recruitment element further comprises a P12 domain of the MMLV gag or a mutant thereof located between (a) and (b). In some cases, the P 12 domain of the MMLV gag or a mutant thereof is a full-length P12 domain of the MMLV gag, a N-terminal fragment of the full-length P12 domain of the MMLV gag, a C-terminal fragment of the full-length P12 domain of the MMLV gag, or a fragment of the full-length P12 domain of the MMLV gag fused to a heterologous particle budding motif. In some cases, the heterologous particle budding motif is RSV P2B or a mutant thereof or a sequence listed in Table 5.

[0140] In some cases, the plasma membrane recruitment element comprises the following configurations arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment:1) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag;2) the N-terminal fragment of the matrix protein of the MMLV gag, a fragment of P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag;3) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag;4) the N-terminal fragment of the matrix protein of the MMLV gag, a fusion of a fragment of P12 domain of the HIV gag and a particle budding motif (e.g., a sequence selected from Table 5), the full-length capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag;5) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag;6) the N-terminal fragment of the matrix protein of the MMLV gag, a fragment of P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag;7) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag;) the N-terminal fragment of the matrix protein of the MMLV gag, a fusion of a fragment of P12 domain of the HIV gag and a particle budding motif (e.g., a sequence selected from Table 5), a C- terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; 0) the N-terminal fragment of the matrix protein of the MMLV gag, a fragment of P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; 1) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; 2) the N-terminal fragment of the matrix protein of the MMLV gag, a fusion of a fragment of P12 domain of the HIV gag and a particle budding motif (e.g., a sequence selected from Table 5), a N-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; 3) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; 4) the N-terminal fragment of the matrix protein of the MMLV gag, a fragment of P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; 5) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; 6) the N-terminal fragment of the matrix protein of the MMLV gag, a fusion of a fragment of P12 domain of the HIV gag and a particle budding motif (e.g., a sequence selected from Table 5), the full-length capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; 7) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; 8) the N-terminal fragment of the matrix protein of the MMLV gag, a fragment of P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag;) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) the N-terminal fragment of the matrix protein of the MMLV gag, a fusion of a fragment of P12 domain of the HIV gag and a particle budding motif (e.g., a sequence selected from Table 5), a C- terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) the N-terminal fragment of the matrix protein of the MMLV gag, a fragment of P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) the N-terminal fragment of the matrix protein of the MMLV gag, a fusion of a fragment of P12 domain of the HIV gag and a particle budding motif (e.g., a sequence selected from Table 5), a N-terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and a leucine zipper; ) the N-terminal fragment of the matrix protein of the MMLV gag, a fragment of P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and a leucine zipper; ) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and a leucine zipper;) the N-terminal fragment of the matrix protein of the MMLV gag, a fusion of a fragment of P12 domain of the HIV gag and a particle budding motif (e.g., a sequence selected from Table 5), the full-length capsid protein of the MMLV gag, and a leucine zipper; ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and a leucine zipper;) the N-terminal fragment of the matrix protein of the MMLV gag, a fragment of P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and a leucine zipper;) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and a leucine zipper;) the N-terminal fragment of the matrix protein of the MMLV gag, a fusion of a fragment of P12 domain of the HIV gag and a particle budding motif (e.g., a sequence selected from Table 5), a C- terminal fragment of the capsid protein of the MMLV gag, and a leucine zipper; ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and a leucine zipper;) the N-terminal fragment of the matrix protein of the MMLV gag, a fragment of P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and a leucine zipper;) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and a leucine zipper; ) the N-terminal fragment of the matrix protein of the MMLV gag, a fusion of a fragment of P12 domain of the HIV gag and a particle budding motif (e.g., a sequence selected from Table 5), a N-terminal fragment of the capsid protein of the MMLV gag, and a leucine zipper; ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag, the full-length nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag, the full-length nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag, the full-length nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag, the full-length nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a C-terminal fragment of the capsid protein of the MMLV gag, the full-length nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a C-terminal fragment of the capsid protein of the MMLV gag, the full-length nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a C-terminal fragment of the capsid protein of the MMLV gag, the full-length nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a C-terminal fragment of the capsid protein of the MMLV gag, the full-length nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5);) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of the capsid protein of the MMLV gag, the full-length nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of the capsid protein of the MMLV gag, the full-length nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of the capsid protein of the MMLV gag, the full-length nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of the capsid protein of the MMLV gag, the full-length nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag, a fragment of the nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag, a fragment of the nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag, a fragment of the nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag, a fragment of the nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a C-terminal fragment of the capsid protein of the MMLV gag, a fragment of the nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a C-terminal fragment of the capsid protein of the MMLV gag, a fragment of the nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a C-terminal fragment of the capsid protein of the MMLV gag, a fragment of the nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a C-terminal fragment of the capsid protein of the MMLV gag, a fragment of the nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5);) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of the capsid protein of the MMLV gag, a fragment of the nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g, a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of the capsid protein of the MMLV gag, a fragment of the nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of the capsid protein of the MMLV gag, a fragment of the nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of the capsid protein of the MMLV gag, a fragment of the nucleocapsid protein of the MMLV gag, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag, a leucine zipper, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag, a leucine zipper, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag, a leucine zipper, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag, a leucine zipper, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a C-terminal fragment of the capsid protein of the MMLV gag, a leucine zipper, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a C-terminal fragment of the capsid protein of the MMLV gag, a leucine zipper, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a C-terminal fragment of the capsid protein of the MMLV gag, a leucine zipper, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a C-terminal fragment of the capsid protein of the MMLV gag, a leucine zipper, and a particle budding motif (e.g., a sequence selected from Table 5);) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of the capsid protein of the MMLV gag, a leucine zipper, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of the capsid protein of the MMLV gag, a leucine zipper, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of the capsid protein of the MMLV gag, a leucine zipper, and a particle budding motif (e.g., a sequence selected from Table 5); ) the N-terminal fragment of the matrix protein of the MMLV gag, a N-terminal fragment of the capsid protein of the MMLV gag, a leucine zipper, and a particle budding motif (e.g., a sequence selected from Table 5); ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a fragment of P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a fusion of a fragment of P12 domain of the HIV gag and a particle budding motif (e.g., a sequence selected from Table 5), the full-length capsid protein of the MMLV gag, and the full- length nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a fragment of P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a fusion of a fragment of P12 domain of the HIV gag and a particle budding motif (e.g., a sequence selected from Table 5), a C-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag;) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a fragment of P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a fusion of a fragment of P12 domain of the HIV gag and a particle budding motif (e.g., a sequence selected from Table 5), a N-terminal fragment of the capsid protein of the MMLV gag, and the full-length nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a fragment of P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of P12 domain of the HIV gag, the full-length capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a fusion of a fragment of P12 domain of the HIV gag and a particle budding motif (e.g., a sequence selected from Table 5), the full-length capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a fragment of P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of P12 domain of the HIV gag, a C-terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a fusion of a fragment of P12 domain of the HIV gag and a particle budding motif (e.g., asequence selected from Table 5), a C-terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), the full-length P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a fragment of P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a mutant thereof (e.g., a sequence selected from Table 4), a N-terminal fragment of P12 domain of the HIV gag, a N-terminal fragment of the capsid protein of the MMLV gag, and a fragment of the nucleocapsid protein of the MMLV gag; ) a pleckstrin homology (PH) domain or a ...

Claims

CLAIMSWhat is claimed is:

1. A lipid delivery particle comprising(a) a lipid membrane;(b) a plasma membrane recruitment element comprising a mutant gag polyprotein, and(c) a payload encapsulated by the lipid containing membrane, and wherein the plasma membrane recruitment element lacks at least a fragment of a matrix protein, at least a fragment of a RNA-binding phosphoprotein, at least a fragment of a capsid protein, a gag -endogenous protease cleavage sequence, or at least a fragment of a nucleocapsid protein; and wherein(1) the plasma membrane recruitment element comprises(i) a full-length capsid protein;(ii) a full-length matrix protein;(iii) a heterologous sequence;(iv) at least a portion of a nucleocapsid protein;(v) two or more particle budding motifs;(vi) at least a portion of a P6 domain; or(vii) two spacer peptides;(2) the lipid delivery particle further comprises an envelope protein, wherein the envelope protein comprises an envelope protein from human endogenous retrovirus (HERV) or a mutant thereof; or(3) the plasma membrane recruitment element is fused to(i) a cleavable linker;(ii) a membrane penetrating peptide; or(iii) a post-translational modification motif.

2. The lipid delivery particle of claim 1, wherein the mutant gag polyprotein is a mutant of a wild-type gag polyprotein of a retrovirus; optionally wherein the retrovirus is oncoretroviruses, lentiviruses, or spumaviruses; optionally wherein the retrovirus is Human Immunodeficiency Virus (HIV), Moloney Murine Leukemia Virus (MMLV), or Rous sarcoma virus (RSV).

3. The lipid delivery particle of claim 1, wherein the mutant gag polyprotein is a mutant of a wild-type gag polyprotein of a human endogenous retrovirus (HERV) or a gag homology protein (optionally human Arc); optionally wherein the HERV is HERV-K or HERV-W; optionally wherein the HERV- K is HERV-K113, HERV-K101, HERV-K102, HERV-K104, HERV-K107, HERV-K108, HERV- K109, HERV-K115, HERV-K1 lp22, or HERV-K12ql3; optionally wherein the mutant gag polyprotein is a mutant of a wild-type gag polyprotein of a HERV-K 113.

4. The lipid delivery particle of claim 1, wherein the mutant gag polyprotein is a mutant of a wild type gag polyprotein of an alpharetrovirus, a betaretrovirus, or a deltaretrovirus, optionally the wild type gag polyprotein comprises the sequence set forth in any one of SEQ ID NOs: 285-298.

5. The lipid delivery particle of any one of claims 1-4, wherein the lipid delivery particle comprises a chimeric protein comprising the plasma membrane recruitment element and the payload.

6. The lipid delivery particle of any one of claims 1-5, wherein the at least a fragment of the matrix protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the matrix protein of a corresponding wild type gag polyprotein.

7. The lipid delivery particle of any one of claims 1-5, wherein the at least a fragment of the matrix protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the matrix protein of a corresponding wild type gag polyprotein.

8. The lipid delivery particle of any one of claims 1-7, wherein the at least a fragment of the RNA- binding phosphoprotein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the RNA -binding phosphoprotein of a corresponding wild type gag polyprotein.

9. The lipid delivery particle of any one of claims 1-7, wherein the at least a fragment of the RNA- binding phosphoprotein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the RNA-binding phosphoprotein of a corresponding wild type gag polyprotein.

10. The lipid delivery particle of any one of claims 1-9, wherein the at least a fragment of the capsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the capsid protein of a corresponding wild type gag polyprotein.11 . The lipid delivery particle of any one of claims 1-9, wherein the at least a fragment of the capsid protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the capsid protein of a corresponding wild type gag polyprotein.

12. The lipid delivery particle of any one of claims 1-11, wherein the at least a fragment of the nucleocapsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the nucleocapsid protein of a corresponding wild type gag polyprotein.

13. The lipid delivery particle of any one of claims 1-11, wherein the at least a fragment of the nucleocapsid protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90,91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the nucleocapsid protein of a corresponding wild type gag polyprotein.

14. The lipid delivery particle of any one of claims 1-13, wherein the at least a portion of the P6 domain comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the P6 domain of the corresponding wild type gag polyprotein.

15. The lipid delivery particle of any one of claims 1-13, wherein the at least a portion of the P6 domain comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the P6 domain of a corresponding wild type gag polyprotein.

16. The lipid delivery particle of any one of claims 1-15, wherein the plasma membrane recruitment element comprises the full-length capsid protein.

17. The lipid delivery particle of any one of claims 1-15, wherein the plasma membrane recruitment element comprises the full-length matrix protein.

18. The lipid delivery particle of any one of claims 1-17, wherein the plasma membrane recruitment element comprises the heterologous sequence; optionally wherein the heterologous sequence is fused to a fragment of the capsid protein, a matrix protein or a fragment thereof, a nucleocapsid protein or a fragment thereof, a particle budding motif or a fragment thereof; optionally wherein the plasma membrane recruitment element lacks the matrix protein; optionally wherein the fragment of the capsid protein is a C-terminal fragment comprising a major homology region (MHR).

19. The lipid delivery particle of claim 18, wherein the heterologous sequence is fused to the N-terminal of the fragment of the capsid protein or a particle budding motif (optionally a late domain of RSV); optionally wherein the heterologous sequence is a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof.

20. The lipid delivery particle of any one of claims 1-19, wherein the plasma membrane recruitment element comprises at least a portion of the nucleocapsid protein; optionally a N-terminal fragment of the nucleocapsid protein; optionally a C-terminal fragment of the nucleocapsid protein).21 . The lipid delivery particle of any one of claims 1-20, wherein the plasma membrane recruitment element comprises two or more particle budding motifs; optionally wherein (a) at least one of the two or more particle budding motifs is endogenous, (b) at least one of the two or more particle budding motifs is heterologous (optionally RSV P2B or a mutant thereof), (c) at least one of the two or more particle budding motifs comprises a PTAP motif, a PPPY motif, a PPXY motif, a YXXL motif, a YPXnL motif, or any combinations thereof, wherein n is an integer from 1 to 5; or (d) at least one of the two or more particle budding motifs comprises a sequence listed in Table 5.

22. The lipid delivery particle of any one of claims 1-2, or 5-21, wherein the plasma membrane recruitment element comprises at least a portion of the P6 domain; optionally wherein the plasma membrane recruitment element comprises at least a N-terminal fragment of the P6 domain or at leasta C-terminal fragment of the P6 domain; optionally wherein the plasma membrane recruitment element comprises the mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of HIV.

23. The lipid delivery particle of any one of claims 1-22, wherein the plasma membrane recruitment element is fused to the post-translational modification motif is selected from the group consisting of: a myristoylation motif, an acetylation motif, an isoprenylation motif, a palmitoylation motif, a famesylation motif, and any combinations thereof.

24. The lipid delivery particle of any one of claims 1-2, or 5-22, wherein the plasma membrane recruitment element comprises the two spacer peptides; optionally wherein at least one of the two spacer peptides is P2 domain or Pl domain; optionally wherein the two spacer peptides are P2 domain and Pl domain; optionally wherein the plasma membrane recruitment element comprises the mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of HIV.

25. The lipid delivery particle of any one of claims 1-24, wherein the lipid delivery particle further comprises the envelope protein, and wherein the envelope protein comprises the envelope protein from human endogenous retrovirus (HERV) or a mutant thereof; optionally wherein the envelope protein comprises hENVHl, hENVH2, hENVH3, hENVKl, hENVK2, hENVK3, hENVK4, hENVK5, hENVK6, hENVT, hENVW, hENVFRD, hENVR, hENVR(b), hENVR(c)2, hENVR(c)l, or hENVKcon, or a mutant thereof.

26. The lipid delivery particle of any one of claims 1-25, wherein the plasma membrane recruitment element is fused to the cleavable linker, and wherein the cleavable linker connects the plasma membrane recruitment element and the payload.

27. The lipid delivery particle of any one of claims 1-26, wherein the plasma membrane recruitment element is fused to the membrane penetrating peptide; optionally wherein (a) the membrane penetrating peptide is linked to the payload or the plasma membrane recruitment element; (b) the membrane penetrating peptide is linked between the payload and the plasma membrane recruitment element; optionally wherein the membrane penetrating peptide comprises a sequence having at least about 80% sequence identity to a sequence listed in Table 6.

28. The lipid delivery particle of any one of claims 1, 2, or 5-15, wherein the mutant gag polyprotein is a mutant of a wild-type gag polyprotein of HIV, and wherein (1) the plasma membrane recruitment element is fused to the cleavable linker, the membrane penetrating peptide, or the post-translational modification motif; or (2) wherein the lipid delivery particle further comprises the envelope protein, and wherein the envelope protein comprises the envelope protein from human endogenous retrovirus (HERV) or a mutant thereof.

29. The lipid delivery particle of claim 28, wherein the plasma membrane recruitment element comprises (a) at least a fragment of matrix protein of an HIV gag, optionally a N-terminal fragment of the matrix protein of the HIV gag; or (b) a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof.

30. The lipid delivery particle of claim 28 or 29, wherein the plasma membrane recruitment element comprises at least a fragment of capsid protein of the HIV gag; optionally wherein the plasmamembrane recruitment element comprises a full-length capsid protein of the HIV gag; optionally wherein the plasma membrane recruitment element comprises a C-terminal fragment of capsid protein of the HIV gag.31 . The lipid delivery particle of any one of claims 28-30, wherein the plasma membrane recruitment element comprises a spacer peptide of the HIV gag; optionally wherein the plasma membrane recruitment element comprises a P2 domain of the HIV gag, a Pl domain of the HIV gag, or both.

32. The lipid delivery particle of any one of claims 28-31, wherein the plasma membrane recruitment element comprises (a) a heterologous domain, optionally wherein the heterologous domain comprises a multimerization motif, optionally wherein the multimerization motif forms parallel homodimers or parallel heterodimers (optional DZF), optionally wherein the parallel homodimers comprise a coiled- coil, optionally wherein the coiled-coil is a leucine zipper, optionally wherein the plasma membrane recruitment element lacks nucleocapsid protein of the HIV gag; or (b) a full-length nucleocapsid protein of the HIV gag or a fragment thereof.

33. The lipid delivery particle of any one of claims 28-32, wherein the plasma membrane recruitment element comprises a particle budding motif; optionally wherein the plasma membrane recruitment element comprises two or more particle budding motifs; optionally wherein at least one of the particle budding motifs is (a) a particle budding motif of the HIV gag (optionally a N-terminal fragment of the P6 domain of the HIV gag, a PTAP motif, or a full-length P6 domain of the HIV gag); or (b) a heterologous particle budding motif (optionally RSV P2B or a mutant thereof or a sequence listed in Table 5).

34. The lipid delivery particle of any one of claims 28-33, wherein the plasma membrane recruitment element lacks a matrix protein of the HIV gag, and wherein the plasma membrane recruitment element comprises a N-terminal myristoylation motif, the full-length capsid protein of the HIV gag or a fragment thereof, the multimerization motif (optionally a DZF), and a heterologous particle budding motif (optionally a late domain of RSV) arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

35. The lipid delivery particle of any one of claims 28-33, wherein the plasma membrane recruitment element lacks a matrix protein of the HIV gag, and wherein the plasma membrane recruitment element comprises a heterologous particle budding motif (optionally a late domain of RSV), a N- terminal myristoylation motif, the full-length capsid protein of the HIV gag or a fragment thereof, the multimerization motif (optionally a DZF), arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

36. The lipid delivery particle of any one of claims 28-33, wherein the plasma membrane recruitment element comprises(a) the N-terminal fragment of the matrix protein of the HIV gag or the pleckstrin homology (PH) domain or a mutant thereof;(b) the full-length capsid protein of the HIV gag or a fragment thereof;(c) the multimerization motif (optionally a leucine zipper) or the full-length nucleocapsid protein of the HIV gag or a fragment thereof; and(d) the particle budding motif; optionally wherein the (a)-(d) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the plasma membrane recruitment element further comprises the P2 domain of the HIV gag located at a position between (b) and (c).

37. The lipid delivery particle of any one of claims 28-33, wherein the plasma membrane recruitment element comprises:(a) the particle budding motif;(b) the N-terminal fragment of the matrix protein of the HIV gag or the pleckstrin homology (PH) domain or a mutant thereof;(c) the full-length capsid protein of the HIV gag or a fragment thereof; and(d) the multimerization motif (optionally a leucine zipper) or the full-length nucleocapsid protein of the HIV gag or a fragment thereof; and; optionally wherein the (a)-(d) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the plasma membrane recruitment element further comprises the P2 domain of the HIV gag located at a position between (c) and (d).

38. The lipid delivery particle of claim 36, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag or a fragment thereof, the P2 domain of the HIV gag, the full-length capsid protein of the HIV gag, the Pl domain of the HIV gag, and the P6 domain of the HIV gag or a fragment thereof, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

39. The lipid delivery particle of claim 36, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag or a fragment thereof, the P2 domain of the HIV gag, the leucine zipper, and the P6 domain of the HIV gag or a fragment thereof, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

40. The lipid delivery particle of claim 36, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag or a fragment thereof, the P2 domain of the HIV gag, the leucine zipper, and a particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.41 . The lipid delivery particle of claim 36, wherein the plasma membrane recruitment element comprises a particle budding motif, the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag or a fragment thereof, the P2 domain of the HIV gag, and the leucinezipper, arranged in order from a N-terminus of the plasma membrane recruitment element to a C- terminus of the plasma membrane recruitment element.

42. The lipid delivery particle of claim 36, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif, a C- terminal fragment of the HIV gag, the P2 domain of the HIV gag, the leucine zipper, and a second particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

43. The lipid delivery particle of claim 36, wherein the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, optionally a first particle budding motif, the full-length capsid protein of the HIV gag or a fragment thereof, optionally the P2 domain of the HIV gag, the leucine zipper, and optionally a second particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

44. The lipid delivery particle of claim 43, wherein the plasma membrane recruitment element comprises the first and the second particle budding motif; optionally wherein each of the first and the second particle budding motifs independently (a) is the particle budding motif of the HIV gag; (b) is a heterologous particle budding motif (optionally RSV P2B or a mutant thereof); or (c) comprises a sequence listed in Table 5.

45. The lipid delivery particle of claim 44, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the heterologous particle budding motif, the full-length capsid protein of the HIV gag, the P2 domain, the leucine zipper, and the particle budding motif of the HIV gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof.

46. The lipid delivery particle of claim 45, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag or the pleckstrin homology (PH) domain or a mutant thereof, the full-length capsid protein of the HIV gag, the P2 domain, the full- length nucleocapsid protein of the HIV gag, and the particle budding motif of the HIV gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof.

47. A lipid delivery particle comprising(a) a lipid membrane;(b) a plasma membrane recruitment element comprising a mutant gag polyprotein that is not from HIV, and(c) a payload encapsulated by the lipid containing membrane,wherein the plasma membrane recruitment element lacks at least a fragment of a matrix protein, at least a fragment of a RNA-binding phosphoprotein, at least a fragment of a capsid protein, a gag- endogenous protease cleavage sequence, or at least a fragment of a nucleocapsid protein.

48. The lipid delivery particle of claim 47, wherein the mutant gag polyprotein is mutant of a wild-type gag polypeptide of a retrovirus; optionally wherein the retrovirus is oncoretroviruses, lentiviruses, or spumaviruses; optionally wherein the retrovirus is MMLV.

49. The lipid delivery particle of claim 47, wherein the mutant gag polyprotein is mutant of a wild-type gag polypeptide of a human endogenous retrovirus (HERV) or a gag homology protein (optionally human Arc or PEG10); optionally wherein the HERV is HERV-K or HERV-W; optionally wherein the HERV-K is HERV-K113, HERV-K101, HERV-K102, HERV-K104, HERV-K107, HERV-K108, HERV-K109, HERV-K115, HERV-K1 lp22, or HERV-K12ql3; optionally wherein the mutant gag polyprotein is mutant of a wild-type gag polypeptide of HERV-K113 or a hGAGKcon.

50. The lipid delivery particle of claim 47, wherein the mutant gag polyprotein is a mutant of a wild type gag polyprotein of an alpharetrovirus, a betaretrovirus, or a deltaretrovirus, optionally the wild type gag polyprotein comprises the sequence set forth in any one of SEQ ID NOs: 285-298.51 . The lipid delivery particle of any one of claims 47-49, wherein the lipid delivery particle comprises a chimeric protein comprising the plasma membrane recruitment element and the payload.

52. The lipid delivery particle of any one of claims 47-51, wherein the at least a fragment of the matrix protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the matrix protein of a corresponding wild type gag polyprotein.

53. The lipid delivery particle of any one of claims 47-51, wherein the at least a fragment of the matrix protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the matrix protein of a corresponding wild type gag polyprotein.

54. The lipid delivery particle of any one of claims 47-53, wherein the at least a fragment of the RNA- binding phosphoprotein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the RNA-binding phosphoprotein of a corresponding wild type gag polyprotein.

55. The lipid delivery particle of any one of claims 47-53, wherein the at least a fragment of the RNA- binding phosphoprotein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the RNA-binding phosphoprotein of a corresponding wild type gag polyprotein.

56. The lipid delivery particle of any one of claims 47-55, wherein the at least a fragment of the capsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%,70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the capsid protein of a corresponding wild type gag polyprotein.

57. The lipid delivery particle of any one of claims 47-55, wherein the at least a fragment of the capsid protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the capsid protein of a corresponding wild type gag polyprotein.

58. The lipid delivery particle of any one of claims 47-57, wherein the at least a fragment of the nucleocapsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the nucleocapsid protein of a corresponding wild type gag polyprotein.

59. The lipid delivery particle of any one of claims 47-57, wherein the at least a fragment of the nucleocapsid protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the nucleocapsid protein of a corresponding wild type gag polyprotein.

60. The lipid delivery particle of any one of claims 1-15, or 47-59, wherein the plasma membrane recruitment element lacks the at least a fragment of a matrix protein; optionally wherein the plasma membrane recruitment element lacks a N-terminal fragment of the matrix protein.61 . The lipid delivery particle of any one of claims 1, 2, 5-15, 47, 48 or 51-60, wherein the plasma membrane recruitment element lacks the at least a fragment of a RNA-binding phosphoprotein; optionally wherein the plasma membrane recruitment element comprises a mutant of a wild-type gag polyprotein of MMLV.

62. The lipid delivery particle of any one of claims 1-3, 5-15, or 47-61, wherein the plasma membrane recruitment element lacks the at least a fragment of a capsid protein; optionally wherein the plasma membrane recruitment element lacks a N-terminal fragment of the capsid protein, a C-terminal fragment of the capsid protein, or both.

63. The lipid delivery particle of any one of claims 1-3, 5-15, or 47-62, wherein the plasma membrane recruitment element lacks the gag -endogenous protease cleavage sequence.

64. The lipid delivery particle of any one of claims 1-3, 5-15, or 47-63, wherein the plasma membrane recruitment element lacks the at least a fragment of a nucleocapsid protein; optionally wherein the plasma membrane recruitment element lacks a N-terminal fragment of the nucleocapsid protein, a C- terminal fragment of the nucleocapsid protein, or both; optionally wherein the plasma membrane recruitment element lacks the nucleocapsid protein.

65. The lipid delivery particle of any one of claims 1-2, 5-21, 23, 25-27, 47-48, or 51-64, wherein the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wildtype gag polyprotein of MMLV.

66. The lipid delivery particle of claim 65, wherein the plasma membrane recruitment element comprises(a) a matrix protein of the MMLV gag (optionally full-length matrix protein of the MMLV gag, a N- terminal fragment or a C-terminal fragment of the full-length matrix protein of the MMLV gag), a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof;(b) a capsid protein of the MMLV gag or a mutant thereof, optionally wherein the capsid protein of the MMLV gag or a mutant thereof is a full-length capsid protein of the MMLV gag, or a N-terminal fragment of or a C-terminal fragment of the full-length capsid protein of the MMLV gag;(c) heterologous domain, optionally wherein the heterologous domain comprises a multimerization motif (optionally a leucine zipper); and(d) an optional particle budding motif, optionally wherein the particle budding motif is particle budding motif of the MMLV gag; optionally wherein the particle budding motif is a heterologous particle budding motif; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof or a sequence listed in Table 5; optionally wherein the (a)-(d) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the plasma membrane recruitment element further comprises a P12 domain of the MMLV gag or a mutant thereof located between (a) and (b), optionally wherein the P 12 domain of the MMLV gag or a mutant thereof is a full-length P12 domain of the MMLV gag, a N-terminal fragment of the full-length P12 domain of the MMLV gag, a C-terminal fragment of the full-length P12 domain of the MMLV gag, or a fragment of the full-length P12 domain of the MMLV gag fused to a heterologous particle budding motif (optionally RSV P2B or a mutant thereof or a sequence listed in Table 5).

67. The lipid delivery particle of claim 66, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the full-length matrix protein of the MMLV gag, the full-length P12 domain of the MMLV gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the MMLV gag or a fragment thereof, and the leucine zipper, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

68. The lipid delivery particle of claim 66, wherein the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length P12 domain of the MMLV gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the MMLV gag or a fragment thereof, the leucine zipper, and optionally the particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

69. The lipid delivery particle of claim 66, wherein the plasma membrane recruitment element comprises the particle budding motif, the pleckstrin homology (PH) domain or a mutant thereof, the full-length P12 domain of the MMLV gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the MMLV gag or a fragment thereof, and the leucine zipper,arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

70. The lipid delivery particle of claim 66, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the full-length matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag or a fragment thereof, the leucine zipper, and the particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.71 . The lipid delivery particle of claim 66, wherein the plasma membrane recruitment element comprises the particle budding motif, the N-terminal fragment of the full-length matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag or a fragment thereof, and the leucine zipper, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

72. The lipid delivery particle of claim 66, wherein the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length capsid protein of the MMLV gag or a fragment thereof, the leucine zipper, and the particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

73. The lipid delivery particle of claim 66, wherein the plasma membrane recruitment element comprises the particle budding motif, the pleckstrin homology (PH) domain or a mutant thereof, the full-length capsid protein of the MMLV gag or a fragment thereof, and the leucine zipper, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

74. The lipid delivery particle of any one of claims 1, 3, 5-21, 23, 25-27, 47, 49, or 51-64, wherein the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wildtype gag polyprotein of hGAGKcon; optionally wherein the plasma membrane recruitment element comprises a N-terminal myristoylation motif of the hGAGKcon gag, a full-length capsid protein of the hGAGKcon gag or a fragment thereof, a multimerization motif (optionally a DZF), and a particle budding motif (optionally a late domain of RSV); optionally wherein the plasma membrane recruitment element comprises a N-terminal myristoylation motif of an HIV gag, a full-length capsid protein of the hGAGKcon gag or a fragment thereof, a multimerization motif (optionally a DZF), and a particle budding motif (optionally a late domain of RSV).

75. The lipid delivery particle of any one of claims 1, 3, 5-21, 23, 25-27, 47, 49, or 51-64, wherein the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wildtype gag polyprotein of HERV-K113.

76. The lipid delivery particle of claim 75, wherein the plasma membrane recruitment element comprises: (a) a matrix protein of the HERV-K113 gag (optionally full-length matrix protein of the HERV-K113 gag, a N-terminal fragment or a C-terminal fragment of the full-length matrix protein of the HERV- K113 gag), a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof;(b) a capsid protein of the HERV-K113 gag or a mutant thereof, optionally wherein the capsid protein of the HERV-K113 gag or a mutant thereof is a full-length capsid protein of the HERV-K113 gag, or a N-terminal fragment of or a C-terminal fragment of the full-length capsid protein of the HERV- K113 gag;(c) heterologous domain, optionally wherein the heterologous domain comprises a multimerization motif (optionally a leucine zipper); and(d) an optional particle budding motif, optionally wherein the particle budding motif is particle budding motif of the HERV-K113 gag; optionally wherein the particle budding motif is a heterologous particle budding motif; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof or a sequence listed in Table 5);(e) an optional QP1 domain of the HERV-K113 gag; and(f) an optional QP2 domain of the HERV-K113 gag; optionally wherein (a)-(f) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the plasma membrane recruitment element further comprises a P15 domain of the HERV-K113 gag or a mutant thereof, optionally wherein the P15 domain of the HERV-K113 gag or a mutant thereof is a full-length P15 domain of the HERV-K113 gag, a N-terminal fragment of the full-length P15 domain of the HERV-K113 gag, a C-terminal fragment of the full-length P15 domain of the HERV-K113 gag, or a fragment of the full-length P15 domain of the HERV-K113 gag fused to a heterologous particle budding motif (optionally RSV P2B or a mutant thereof or a sequence listed in Table 5).

77. The lipid delivery particle of claim 76, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the full-length matrix protein of the HERV-K113 gag, the full-length P15 domain of the HERV-K113 gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, the optional QP1 domain of the HERV-K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C- terminus of the plasma membrane recruitment element.

78. The lipid delivery particle of claim 76, wherein the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length P15 domain of the HERV- K113 gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, optionally the particle budding motif, the optional QP1 domain of the HERV-K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

79. The lipid delivery particle of claim 76, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the full-length matrix protein of the HERV-K113 gag, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, the particle buddingmotif, the optional QP1 domain of the HERV-K113 gag, and the optional QP2 domain of the HERV- K1 13 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C- terminus of the plasma membrane recruitment element.

80. The lipid delivery particle of claim 76, wherein the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, the particle budding motif, the optional QP1 domain of the HERV-K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.81 . The lipid delivery particle of any one of claims 76-80, wherein the plasma membrane recruitment element comprises the QP1 domain and the QP2 domain of the HERV-K113 gag.

82. The lipid delivery particle of any one of claims 1-2, 5-21, 23, 25-27, 47, 48, or 51-64, wherein the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wildtype gag polyprotein of RSV; optionally wherein the plasma membrane recruitment element comprises a matrix protein of the RSV gag and a late domain of the RSV gag; optionally wherein the plasma membrane recruitment element comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a full-length nucleocapsid protein of the RSV; optionally wherein the plasma membrane recruitment element comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a fragment of the nucleocapsid protein of the RSV; optionally wherein the plasma membrane recruitment element further comprises a N-terminal myristoylation motif.

83. The lipid delivery particle of any one of claims 28-46 or 65-82, wherein the plasma membrane recruitment element comprises one, two, or three particle budding motif, wherein each of the particle budding motif is selected from a sequence listed in Table 5.

84. The lipid delivery particle of any one of claims 1-83, wherein the plasma membrane recruitment element comprises a major homology region (MHR).

85. The lipid delivery particle of any one of claims 1-17, or 20-84, wherein the plasma membrane recruitment element comprises the heterologous sequence; optionally wherein the heterologous sequence is fused to a fragment of the matrix protein, optionally the N-terminal of the fragment of the matrix protein; optionally wherein the heterologous sequence is a pleckstrin homology (PH) domain or a mutant thereof; optionally wherein the PH domain is a human PH domain; optionally wherein the fragment of the matrix protein lacks a N-terminal myristoylation motif, a N-terminal glycine, a highly basic region (HBR), a N-terminal fragment, or any combination thereof.

86. The lipid delivery particle of any one of claims 5-46, or 51-85, wherein the chimeric protein comprises a cleavable linker; optionally wherein the cleavable linker connects the plasma membrane recruitment element and the payload.

87. The lipid delivery particle of any one of claims 5-46, or 51-86, wherein the chimeric protein comprises a nuclear localization signal (NLS) sequence.

88. The lipid delivery particle of any one of claims 5-46, or 51-87, wherein the chimeric protein comprises a nuclear export signal (NES) sequence.

89. The lipid delivery particle of any one of claims 5-46, or 51-88, wherein the chimeric protein comprises the membrane penetrating peptide, optionally wherein (a) the membrane penetrating peptide is linked to the payload or the plasma membrane recruitment element; or (b) the membrane penetrating peptide connects the payload and the plasma membrane recruitment element; optionally wherein the membrane penetrating peptide comprises a sequence having at least about 80% sequence identity to a sequence listed in Table 6.

90. The lipid delivery particle of any one of claims 5-46, or 51-89, wherein the chimeric protein comprises the post-translational modification motif that is fused directly to (a) the payload; or (b) the plasma membrane recruitment element; optionally wherein the post-translational modification motif comprises a myristoylation motif, an acetylation motif, an isoprenylation motif, a palmitoylation motif, a famesylation motif, or combinations thereof.91 . The lipid delivery particle of any one of claims 5-46, or 51-90, wherein the chimeric protein comprises the plasma membrane recruitment element, an optional NLS, the cleavable linker, and the payload arranged in order from N-terminus of the chimeric protein to C-terminus of the chimeric protein.

92. The lipid delivery particle of any one of claims 26-91, wherein the lipid delivery particle comprises the envelope protein; optionally wherein the envelope protein is a retroviral envelope protein or a mutant thereof; optionally wherein the envelope protein is an envelope protein from human endogenous retrovirus (HERV) or a mutant thereof.

93. The lipid delivery particle of any one of claims 1-92, wherein the plasma membrane recruitment element forms part of a basic structure of the lipid delivery particle (optionally a protein core).

94. The lipid delivery particle of any one of claims 1-93, wherein the payload comprises an antibody, a cytokine, a therapeutic protein, a small molecule therapeutics, a therapeutic DNA, and a therapeutic RNA, a ribonucleoprotein, a zinc-finger, a transcription activator-like effector (TALE), or a CRISPR- based genome editor, or any combinations thereof; optionally wherein the payload comprises a NLS, optionally wherein the NLS is an endogenous NLS or a heterologous NLS.

95. The lipid delivery particle of any one of claims 1-94, wherein the lipid delivery particle further comprises a second plasma membrane recruitment element; optionally wherein the second plasma membrane recruitment element is the same as the plasma membrane recruitment element; optionally wherein the second plasma membrane recruitment element is a retroviral gag or a mutant thereof, a HERV gag or a mutant thereof, a pleckstrin homology (PH) domain or a mutant thereof, or a membrane protein or a transmembrane domain thereof or a mutant thereof.

96. The lipid delivery particle of claim 95, wherein the second plasma membrane recruitment element forms part of a basic structure of the lipid delivery particle (optionally a protein core).

97. The lipid delivery particle of claim 1-96, wherein the lipid delivery particle further comprises a protease; optionally wherein the protease is a retroviral protease.

98. The lipid delivery particle of claim 97, wherein the plasma membrane recruitment element is linked to the protease, optionally via a cleavable linker.

99. The lipid delivery particle of claim 97, wherein the second plasma membrane recruitment element is linked to the protease, optionally via a cleavable linker.

100. The lipid delivery particle of any one of claims 1-99, wherein the plasma membrane recruitment element further comprises one or more mutant gag -endogenous protease cleavage sequences relative to a corresponding wildtype gag-endogenous protease cleavage sequence, and wherein the one or more mutant o gag-endogenous protease cleavage sequences have higher cleavage efficiency than that of the corresponding wildtype gag -endogenous protease cleavage sequence.

101. A recombinant protein comprising a plasma membrane recruitment element comprising a mutant gag polyprotein, wherein the plasma membrane recruitment element lacks at least a fragment of a matrix protein, at least a fragment of a RNA-binding phosphoprotein, at least a fragment of a capsid protein, a gag -endogenous protease cleavage sequence, or at least a fragment of a nucleocapsid protein; and wherein(1) the plasma membrane recruitment element comprises(i) a full-length capsid protein;(ii) a full-length matrix protein;(iii) a heterologous sequence;(iv) at least a portion of a nucleocapsid protein;(v) two or more particle budding motifs;(vi) at least a portion of a P6 domain; or(vii) two spacer peptides; or(2) the plasma membrane recruitment element is fused to(i) a cleavable linker;(ii) a membrane penetrating peptide; or(iii) a post-translational modification motif.

102. The recombinant protein of claim 101, wherein the mutant gag polyprotein is a mutant of a wildtype gag polyprotein of a retrovirus; optionally wherein the retrovirus is oncoretroviruses, lentiviruses, or spumaviruses; optionally wherein the retrovirus is Human Immunodeficiency Virus (HIV), Moloney Murine Leukemia Virus (MMMLV), or Rous sarcoma virus (RSV).

103. The recombinant protein of claim 101, wherein the mutant gag polyprotein is a mutant of a wildtype gag polyprotein of a human endogenous retrovirus (HERV); optionally wherein the HERV is HERV-K or HERV-W; optionally wherein the HERV-K is HERV-K113, HERV-K101, HERV- K102, HERV-K104, HERV-K107, HERV-K108, HERV-K109, HERV-K115, HERV-K1 lp22, or HERV-K12ql3; optionally wherein the mutant gag polyprotein is a mutant of a wild-type gag polyprotein of a HERV-K 113.

104. The recombinant protein of claim 101, wherein the mutant gag polyprotein is a mutant of a wild type gag polyprotein of an alpharetrovirus, a betaretrovirus, or a deltaretrovirus, optionally the wild type gag polyprotein comprises the sequence set forth in any one of SEQ ID NOs: 285-298.

105. The recombinant protein of any one of claims 101-104, wherein the at least a fragment of the matrix protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the matrix protein of a corresponding wild type gag polyprotein.

106. The recombinant protein of any one of claims 101-104, wherein the at least a fragment of the matrix protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the matrix protein of a corresponding wild type gag polyprotein.

107. The recombinant protein of any one of claims 101-106, wherein the at least a fragment of the RNA-binding phosphoprotein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the RNA-binding phosphoprotein of a corresponding wild type gag polyprotein.

108. The recombinant protein of any one of claims 101-106, wherein the at least a fragment of the RNA-binding phosphoprotein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the RNA-binding phosphoprotein of a corresponding wild type gag polyprotein.

109. The recombinant protein of any one of claims 101-108, wherein the at least a fragment of the capsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the capsid protein of a corresponding wild type gag polyprotein.

110. The recombinant protein of any one of claims 101-108, wherein the at least a fragment of the capsid protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the capsid protein of a corresponding wild type gag polyprotein.

111. The recombinant protein of any one of claims 101-110, wherein the at least a fragment of the nucleocapsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the nucleocapsid protein of a corresponding wild type gag polyprotein.

112. The recombinant protein of any one of claims 101-110, wherein the at least a fragment of the nucleocapsid protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the nucleocapsid protein of a corresponding wild type gag polyprotein.

113. The recombinant protein of any one of claims 101-112, wherein the at least a portion of the P6 domain comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the P6 domain of the corresponding wild type gag polyprotein.

114. The recombinant protein of any one of claims 101-112, wherein the at least a portion of the P6 domain comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the P6 domain of a corresponding wild type gag polyprotein.

115. The recombinant protein of any one of claims 101-114, wherein the plasma membrane recruitment element comprises the full-length capsid protein.

116. The recombinant protein of any one of claims 101-114, wherein the plasma membrane recruitment element comprises the full-length matrix protein.

117. The recombinant protein of any one of claims 101-116, wherein the plasma membrane recruitment element comprises the heterologous sequence; optionally wherein the heterologous sequence is fused to a fragment of the capsid protein, a matrix protein or a fragment thereof, a nucleocapsid protein or a fragment thereof, a particle budding motif or a fragment thereof; optionally wherein the plasma membrane recruitment element lacks the matrix protein; optionally wherein the fragment of the capsid protein is a C-terminal fragment.

118. The recombinant protein of claim 117, wherein the heterologous sequence is fused to the N- terminal of the fragment of the capsid protein or a particle budding motif (optionally a late domain of RSV); optionally wherein the heterologous sequence is a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof.

119. The recombinant protein of any one of claims 101-118, wherein the plasma membrane recruitment element comprises at least a portion of a nucleocapsid protein; optionally a N-terminal fragment of the nucleocapsid protein; optionally a C-terminal fragment of the nucleocapsid protein).

120. The recombinant protein or the lipid delivery particle of any one of claims 101-119, wherein the plasma membrane recruitment element comprises two or more particle budding motifs; optionally wherein (a) at least one of the two or more particle budding motifs is endogenous, (b) at least one of the two or more particle budding motifs is heterologous (optionally RSV P2B or a mutant thereof), (c) at least one of the two or more particle budding motifs comprises a PTAP motif, a PPPY motif, a PPXY motif, a YXXL motif, a YPXnL motif, or any combinations thereof, wherein n is an integer from 1 to 5, or (d) at least one of the two or more particle budding motifs comprises a sequence listed in Table 5.

121. The recombinant protein of any one of claims 101, 102, or 105-120, wherein the plasma membrane recruitment element comprises at least a portion of the P6 domain; optionally wherein the plasma membrane recruitment element comprises at least a N-terminal fragment of the P6 domain or at least a C-terminal fragment of the P6 domain; optionally wherein the plasma membranerecruitment element comprises the mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of HIV.

122. The recombinant protein of any one of claims 101-121, wherein the plasma membrane recruitment element is fused to the post-translational modification motif is selected from the group consisting of: a myristoylation motif, an acetylation motif, an isoprenylation motif, a palmitoylation motif, and a famesylation motif.

123. The recombinant protein of any one of claims 101, 102, or 105-121, wherein the plasma membrane recruitment element comprises the two spacer peptides; optionally wherein at least one of the two spacer peptides is P2 domain or P 1 domain; optionally wherein the two spacer peptides are P2 domain and Pl domain; optionally wherein the plasma membrane recruitment element comprises the mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of HIV.

124. The recombinant protein of any one of claims 101-123, wherein the recombinant protein further comprises the envelope protein, and wherein the envelope protein comprises the envelope protein from human endogenous retrovirus (HERV) or a mutant thereof; optionally wherein the envelope protein comprises hENVHl, hENVH2, hENVH3, hENVKl, hENVK2, hENVK3, hENVK4, hENVK5, hENVK6, hENVT, hENVW, hENVFRD, hENVR, hENVR(b), hENVR(c)2, hENVR(c)l, or hENVKcon, or a mutant thereof.

125. The recombinant protein of any one of claims 101-124, wherein the plasma membrane recruitment element is fused to the membrane penetrating peptide; optionally wherein the membrane penetrating peptide is linked to the plasma membrane recruitment element; optionally wherein the membrane penetrating peptide comprises a sequence having at least about 80% sequence identity to a sequence listed in Table 6.

126. The recombinant protein of claim 101, 122, or 124, wherein the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of HIV and wherein (1) the plasma membrane recruitment element is fused to the cleavable linker or the membrane penetrating peptide; or (2) wherein the recombinant protein further comprises the envelope protein, wherein the envelope protein comprises the envelope protein from human endogenous retrovirus (HERV) or a mutant thereof.

127. The recombinant protein of claim 126, wherein the plasma membrane recruitment element comprises (a) at least a fragment of matrix protein of an HIV gag, optionally a N-terminal fragment of the matrix protein of the HIV gag; or (b) a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof.

128. The recombinant protein of claim 126 or 127, wherein the plasma membrane recruitment element comprises at least a fragment of capsid protein of the HIV gag; optionally wherein the plasma membrane recruitment element comprises a full-length capsid protein of the HIV gag; optionally wherein the plasma membrane recruitment element comprises a C-terminal fragment of capsid protein of the HIV gag.

129. The recombinant protein of any one of claims 126-128, wherein the plasma membrane recruitment element comprises a spacer peptide of the HIV gag; optionally wherein the plasma membrane recruitment element comprises a P2 domain of the HIV gag, a Pl domain of the HIV gag, or both.

130. The recombinant protein of any one of claims 126-129, wherein the plasma membrane recruitment element comprises (a) a heterologous domain, optionally wherein the heterologous domain comprises a multimerization motif, optionally wherein the multimerization motif forms parallel homodimers or parallel heterodimers (optional DZF), optionally wherein the parallel homodimers comprise a coiled-coil, optionally wherein the coiled-coil is a leucine zipper, optionally wherein the plasma membrane recruitment element lacks nucleocapsid protein of the HIV gag; or (b) a full-length nucleocapsid protein of the HIV gag or a fragment thereof.

131. The recombinant protein of any one of claims 126-130, wherein the plasma membrane recruitment element comprises a particle budding motif; optionally wherein the plasma membrane recruitment element comprises two or more particle budding motifs; optionally wherein at least one of the particle budding motifs is (a) a particle budding motif of the HIV gag (optionally a N-terminal fragment of the P6 domain of the HIV gag, a PTAP motif, or a full-length P6 domain of the HIV gag); or (b) a heterologous particle budding motif (optionally RSV P2B or a mutant thereof or a sequence listed in Table 5).

132. The recombinant protein of any one of claims 126-131, wherein the plasma membrane recruitment element lacks a matrix protein of the HIV gag and wherein the plasma membrane recruitment element comprises a N-terminal myristoylation motif, the full-length capsid protein of the HIV gag or a fragment thereof, the multimerization motif (optionally a DZF), and a heterologous particle budding motif (optionally a late domain of RSV) arranged in order from aN-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

133. The recombinant protein of any one of claims 126-131, wherein the plasma membrane recruitment element comprises(a) the N-terminal fragment of the matrix protein of the HIV gag or the pleckstrin homology (PH) domain or a mutant thereof;(b) the full-length capsid protein of the HIV gag or a fragment thereof;(c) optionally the P2 domain of the HIV gag;(d) the multimerization motif (optionally a leucine zipper) or the full-length nucleocapsid protein of the HIV gag or a fragment thereof; and(e) the particle budding motif; optionally wherein the (a)-(e) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

134. The recombinant protein of claim 133, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag or a fragment thereof, the P2 domain of the HIV gag, the full-length capsid protein ofthe HIV gag, the P 1 domain of the HIV gag, and the P6 domain of the HIV gag or a fragment thereof, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

135. The recombinant protein of claim 133, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag or a fragment thereof, the P2 domain of the HIV gag, the leucine zipper, and the P6 domain of the HIV gag or a fragment thereof, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

136. The recombinant protein of claim 133, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the full-length capsid protein of the HIV gag or a fragment thereof, the P2 domain of the HIV gag, the leucine zipper, and a particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

137. The recombinant protein of claim 133, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, a first particle budding motif, a C-terminal fragment of the HIV gag, the P2 domain of the HIV gag, the leucine zipper, and a second particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

138. The recombinant protein of claim 133, wherein the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, optionally a first particle budding motif, the full-length capsid protein of the HIV gag or a fragment thereof, optionally the P2 domain of the HIV gag, the leucine zipper, and optionally a second particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

139. The recombinant protein of claim 138, wherein the plasma membrane recruitment element comprises the first and the second particle budding motif; optionally wherein each of the first and the second particle budding motifs independently (a) is the particle budding motif of the HIV gag; (b) is a heterologous particle budding motif (optionally RSV P2B or a mutant thereof); or (c) comprises a sequence listed in Table 5.

140. The recombinant protein of claim 139, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag, the heterologous particle budding motif, the full-length capsid protein of the HIV gag, the P2 domain, the leucine zipper, and the particle budding motif of the HIV gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof.

141. The recombinant protein of claim 133, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the matrix protein of the HIV gag or the pleckstrin homology (PH) domain or a mutant thereof, the full-length capsid protein of the HIV gag, the P2 domain, thefull-length nucleocapsid protein of the HIV gag, and the particle budding motif of the HIV gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof.

142. A recombinant protein comprising a plasma membrane recruitment element comprising a mutant gag polyprotein that is not from HIV, and wherein the plasma membrane recruitment element lacks at least a fragment of a matrix protein, at least a fragment of a RNA-binding phosphoprotein, at least a fragment of a capsid protein, a gag -endogenous protease cleavage sequence, or at least a fragment of a nucleocapsid protein.

143. The recombinant protein of claim 142, wherein the mutant gag polyprotein is mutant of a wildtype gag polypeptide of a retrovirus; optionally wherein the retrovirus is oncoretroviruses, lentiviruses, or spumaviruses; optionally wherein the retrovirus is MMLV or RSV.

144. The recombinant protein of claim 142, wherein the mutant gag polyprotein is mutant of a wildtype gag polypeptide of a human endogenous retrovirus (HERV) or a gag homology protein (optionally human Arc); optionally wherein the HERV is HERV-K or HERV-W; optionally wherein the HERV-K is HERV-K113, HERV-K101, HERV-K102, HERV-K104, HERV-K107, HERV-K108, HERV-K109, HERV-K115, HERV-K1 lp22, or HERV-K12ql3; optionally wherein the mutant gag polyprotein is mutant of a wild-type gag polypeptide of HERV-K113 or a hGAGKcon.

145. The recombinant protein of claim 142, wherein the mutant gag polyprotein is mutant of a wildtype gag polypeptide of an alpharetrovirus, a betaretrovirus, or a deltaretrovirus, optionally the wild type gag polyprotein comprises the sequence set forth in any one of SEQ ID NOs: 285-298.

146. The recombinant protein of any one of claims 142-145, wherein the at least a fragment of the matrix protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the matrix protein of a corresponding wild type gag polyprotein.

147. The recombinant protein of any one of claims 142-145, wherein the at least a fragment of the matrix protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the matrix protein of a corresponding wild type gag polyprotein.

148. The recombinant protein of any one of claims 142-147, wherein the at least a fragment of the RNA-binding phosphoprotein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the RNA-binding phosphoprotein of a corresponding wild type gag polyprotein.

149. The recombinant protein of any one of claims 142-147, wherein the at least a fragment of the RNA-binding phosphoprotein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or morecontiguous amino acid residues of the RNA-binding phosphoprotein of a corresponding wild type gag polyprotein.

150. The recombinant protein of any one of claims 142-149, wherein the at least a fragment of the capsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the capsid protein of a corresponding wild type gag polyprotein.

151. The recombinant protein of any one of claims 142-149, wherein the at least a fragment of the capsid protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the capsid protein of a corresponding wild type gag polyprotein.

152. The recombinant protein of any one of claims 142-151, wherein the at least a fragment of the nucleocapsid protein comprises at least 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the entire amino acid sequence of the nucleocapsid protein of a corresponding wild type gag polyprotein.

153. The recombinant protein of any one of claims 142-151, wherein the at least a fragment of the nucleocapsid protein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 91, 92, 94, 95, 96, 97, 98, 99, 100, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more contiguous amino acid residues of the nucleocapsid protein of a corresponding wild type gag polyprotein.

154. The recombinant protein of any one of claims 101-114, or 142-153, wherein the plasma membrane recruitment element lacks the at least a fragment of a matrix protein; optionally wherein the plasma membrane recruitment element lacks a N-terminal fragment of the matrix protein.

155. The recombinant protein of any one of claims 101-114, 142, 143, or 144-154, wherein the plasma membrane recruitment element lacks the at least a fragment of a RNA-binding phosphoprotein; optionally wherein the plasma membrane recruitment element comprises a mutant of a wild-type gag polyprotein of MMLV.

156. The recombinant protein of any one of claims 101-114, or 142-155, wherein the plasma membrane recruitment element lacks the at least a fragment of a capsid protein; optionally wherein the plasma membrane recruitment element lacks a N-terminal fragment of the capsid protein, a C- terminal fragment of the capsid protein, or both.

157. The recombinant protein of any one of claims 101-114, or 142-156, wherein the plasma membrane recruitment element lacks the gag -endogenous protease cleavage sequence.

158. The recombinant protein of any one of claims 101-114, or 142-157, wherein the plasma membrane recruitment element lacks the at least a fragment of a nucleocapsid protein; optionally wherein the plasma membrane recruitment element lacks a N-terminal fragment of the nucleocapsid protein, a C-terminal fragment of the nucleocapsid protein, or both; optionally wherein the plasma membrane recruitment element lacks the nucleocapsid protein.

159. The recombinant protein of any one of claims 101, 102, 105-114, 115-120, 122, 124-125, 142- 143, or 144-158, wherein the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of MMLV.

160. The recombinant protein of claim 159, wherein the plasma membrane recruitment element comprises(a) a matrix protein of the MMLV gag (optionally full-length matrix protein of the MMLV gag, a N- terminal fragment or a C-terminal fragment of the full-length matrix protein of the MMLV gag), a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof;(b) a capsid protein of the MMLV gag or a mutant thereof, optionally wherein the capsid protein of the MMLV gag or a mutant thereof is a full-length capsid protein of the MMLV gag, or a N-terminal fragment of or a C-terminal fragment of the full-length capsid protein of the MMLV gag;(c) heterologous domain, optionally wherein the heterologous domain comprises a multimerization motif (optionally a leucine zipper); and(d) an optional particle budding motif, optionally wherein the particle budding motif is particle budding motif of the MMLV gag; optionally wherein the particle budding motif is a heterologous particle budding motif; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof or a sequence listed in Table 5; optionally wherein the (a)-(d) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the plasma membrane recruitment element further comprises a P12 domain of the MMLV gag or a mutant thereof located between (a) and (b), optionally wherein the P 12 domain of the MMLV gag or a mutant thereof is a full-length P12 domain of the MMLV gag, a N-terminal fragment of the full-length P12 domain of the MMLV gag, a C-terminal fragment of the full-length P12 domain of the MMLV gag, or a fragment of the full-length P12 domain of the MMLV gag fused to a heterologous particle budding motif (optionally RSV P2B or a mutant thereof or a sequence listed in Table 5).

161. The recombinant protein of claim 159, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the full-length matrix protein of the MMLV gag, the full-length P12 domain of the MMLV gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the MMLV gag or a fragment thereof, and the leucine zipper, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

162. The recombinant protein of claim 159, wherein the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length P12 domain of the MMLV gag or a fragment there of that is fused to a heterologous particle budding motif, the full- length capsid protein of the MMLV gag or a fragment thereof, the leucine zipper, and optionally the particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

163. The recombinant protein of claim 159, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the full-length matrix protein of the MMLV gag, the full-length capsid protein of the MMLV gag or a fragment thereof, the leucine zipper, and the particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C- terminus of the plasma membrane recruitment element.

164. The recombinant protein of claim 159, wherein the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length capsid protein of the MMLV gag or a fragment thereof, the leucine zipper, and the particle budding motif, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

165. The recombinant protein of any one of claims 101, 103-120, 122, 124-125, 142, or 144-158, wherein the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of hGAGKcon; optionally wherein the plasma membrane recruitment element comprises a matrix protein of the RSV gag and a late domain of the RSV gag; optionally wherein the plasma membrane recruitment element comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a full-length nucleocapsid protein of the RSV gag; optionally wherein the plasma membrane recruitment element comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a fragment of the nucleocapsid protein of the RSV; optionally wherein the plasma membrane recruitment element further comprises a N-terminal myristoylation motif of the RSV gag.

166. The recombinant protein of any one of claims 101, 103-120, 122, 124-125, 142, or 144-158, wherein the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of HERV-K113.

167. The recombinant protein of claim 166, wherein the plasma membrane recruitment element comprises(a) a matrix protein of the HERV-K113 gag (optionally full-length matrix protein of the HERV-K113 gag, a N-terminal fragment or a C-terminal fragment of the full-length matrix protein of the HERV- K113 gag), a pleckstrin homology (PH) domain (optionally a human PH domain) or a mutant thereof;(b) a capsid protein of the HERV-K113 gag or a mutant thereof, optionally wherein the capsid protein of the HERV-K113 gag or a mutant thereof is a full-length capsid protein of the HERV-K113 gag, or a N-terminal fragment of or a C-terminal fragment of the full-length capsid protein of the HERV- K113 gag;(c) heterologous domain, optionally wherein the heterologous domain comprises a multimerization motif (optionally a leucine zipper); and(d) an optional particle budding motif, optionally wherein the particle budding motif is particle budding motif of the HERV-K113 gag; optionally wherein the particle budding motif is a heterologous particle budding motif; optionally wherein the heterologous particle budding motif is RSV P2B or a mutant thereof or a sequence listed in Table 5);(e) an optional QP1 domain of the HERV-K113 gag; and(f) an optional QP2 domain of the HERV-K113 gag; optionally wherein (a)-(f) are arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element; optionally wherein the plasma membrane recruitment element further comprises a P15 domain of the HERV-K113 gag or a mutant thereof, optionally wherein the P15 domain of the HERV-K113 gag or a mutant thereof is a full-length P15 domain of the HERV-K113 gag, a N-terminal fragment of the full-length P15 domain of the HERV-K113 gag, a C-terminal fragment of the full-length P15 domain of the HERV-K113 gag, or a fragment of the full-length P15 domain of the HERV-K113 gag fused to a heterologous particle budding motif (optionally RSV P2B or a mutant thereof or a sequence listed in Table 5).

168. The recombinant protein of claim 167, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the full-length matrix protein of the HERV-K113 gag, the full- length Pl 5 domain of the HERV-K113 gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, the optional QP1 domain of the HERV-K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

169. The recombinant protein of claim 167, wherein the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length P15 domain of the HERV-K113 gag or a fragment there of that is fused to a heterologous particle budding motif, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, optionally the particle budding motif, the optional QP1 domain of the HERV-K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

170. The recombinant protein of claim 167, wherein the plasma membrane recruitment element comprises the N-terminal fragment of the full-length matrix protein of the HERV-K113 gag, the full- length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, the particle budding motif, the optional QP1 domain of the HERV-K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

171. The recombinant protein of claim 167, wherein the plasma membrane recruitment element comprises the pleckstrin homology (PH) domain or a mutant thereof, the full-length capsid protein of the HERV-K113 gag or a fragment thereof, the leucine zipper, the particle budding motif, the optional QP1 domain of the HERV-K113 gag, and the optional QP2 domain of the HERV-K113 gag, arranged in order from a N-terminus of the plasma membrane recruitment element to a C-terminus of the plasma membrane recruitment element.

172. The recombinant protein of any one of claims 167-171, wherein the plasma membrane recruitment element comprises the QP1 domain and the QP2 domain of the HERV-K113 gag.

173. The recombinant protein of any one of claims 101-102, 115-120, 122, 124-125, 142-143, or 144- 158, wherein the plasma membrane recruitment element comprises a mutant gag polyprotein that is a mutant of a wild-type gag polyprotein of RSV; optionally wherein the mutant gag polyprotein comprises a matrix protein of the RSV gag and a late domain of the RSV gag; optionally wherein the mutant gag polyprotein comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a full-length nucleocapsid protein of the RSV; optionally wherein the mutant gag polyp rotein comprises a matrix protein of the RSV gag, a late domain of the RSV gag, and a fragment of the nucleocapsid protein of the RSV; optionally wherein the mutant gag polyprotein comprises a N- terminal myristoylation motif of the RSV gag.

174. The recombinant protein of any one of claims 126-141 or 159-173, wherein the plasma membrane recruitment element comprises one, two, or three particle budding motif, wherein each of the particle budding motif is selected from a sequence listed in Table 5.

175. The recombinant protein of any one of claims 117-174, wherein the plasma membrane recruitment element comprises a MHR.

176. The recombinant protein of any one of claims 101-117, or 120-175, wherein the plasma membrane recruitment element comprises the heterologous sequence; optionally wherein the heterologous sequence is fused to at least a fragment of the matrix protein, optionally the N-terminal of the fragment of the matrix protein; optionally wherein the heterologous sequence is a pleckstrin homology (PH) domain or a mutant thereof; optionally wherein the PH domain is a human PH domain; optionally wherein the fragment of the matrix protein lacks a N-terminal myristoylation motif, a N-terminal glycine, a highly basic region (HBR), a N-terminal fragment, or any combinations thereof.

177. The recombinant protein of any one of claims 101-176, wherein the plasma membrane recruitment element further comprises one or more mutant gag -endogenous protease cleavage sequences relative to a corresponding wildtype gag-endogenous protease cleavage sequence, and wherein the one or more mutant gag-endogenous protease cleavage sequences have higher cleavage efficiency than that of the corresponding wildtype gag -endogenous protease cleavage sequence.

178. A chimeric protein comprising the recombinant protein of any one of 101-177, wherein the chimeric protein comprises a cleavable linker; optionally wherein the cleavable linker connects the plasma membrane recruitment element and a payload.

179. The chimeric protein of claim 178, wherein the chimeric protein comprises a nuclear localization signal (NLS) sequence.

180. The chimeric protein of claim 178 or 179, wherein the chimeric protein comprises a nuclear export signal (NES) sequence.

181. The chimeric protein of any one of claims 178-180, wherein the chimeric protein comprises the membrane penetrating peptide, optionally wherein (a) the membrane penetrating peptide is linked tothe payload or the plasma membrane recruitment element; or (b) the membrane penetrating peptide connects the payload and the plasma membrane recruitment element; optionally wherein the membrane penetrating peptide comprises a sequence having at least about 80% sequence identity to a sequence listed in Table 6.

182. The chimeric protein of any one of claims 178-181, wherein the chimeric protein comprises a post-translational modification motif that is fused directly to (a) the payload; or (b) the plasma membrane recruitment element; optionally wherein the post-translational modification motif comprises a myristoylation motif, an acetylation motif, an isoprenylation motif, a palmitoylation motif, a famesylation motif, or combinations thereof.

183. The chimeric protein of any one of claims 178-182, wherein the chimeric protein comprises the plasma membrane recruitment element, an optional NLS, the cleavable linker, and the payload arranged in order from N-terminus of the chimeric protein to C-terminus of the chimeric protein.

184. The chimeric protein of any one of claims 178-183, wherein the payload comprises an antibody, a cytokine, a therapeutic protein, a small molecule therapeutics, a therapeutic DNA, and a therapeutic RNA, a ribonucleoprotein, a zinc-finger, a transcription activator-like effector (TALE), or a CRISPR- based genome editor, or any combinations thereof; optionally wherein the payload comprises a NLS, optionally wherein the NLS is an endogenous NLS or a heterologous NLS.

185. A composition comprising a first nucleic acid sequence encoding the recombinant protein of any one of claims 101-177 or the chimeric protein of any one of claims 178-183.

186. The composition of claim 185, wherein the composition comprises a second nucleic acid sequence encoding an envelope protein; optionally wherein the envelope protein is a retroviral envelope protein or a mutant thereof; optionally wherein the envelope protein is an envelope protein from human endogenous retrovirus (HERV) or a mutant thereof.

187. The composition of claim 185 or 186, wherein the composition further comprises a third nucleic acid sequence encoding a second plasma membrane recruitment element; optionally wherein the second plasma membrane recruitment element is the same as the plasma membrane recruitment element; optionally wherein the second plasma membrane recruitment element is a retroviral gag or a mutant thereof, a HERV gag or a mutant thereof, a pleckstrin homology (PH) domain or a mutant thereof, or a membrane protein or a transmembrane domain thereof or a mutant thereof.

188. The composition of any one of claims 185-187, wherein the composition further comprises fourth nucleic acid encoding a protease; optionally wherein the protease is a retroviral protease.

189. The composition of claim 188, wherein the plasma membrane recruitment element is linked to the protease, optionally via a cleavable linker.

190. The composition of claim 188, wherein the second plasma membrane recruitment element is linked to the protease, optionally via a cleavable linker.

191. A system comprising the lipid delivery particle of any one of claims 1-100 or the composition of any one of claims 185-190.

192. The system of claim 191, wherein the system comprises a producer cell, a cell -free extract, or a cell lysate.

193. A pharmaceutical composition comprising (a) the lipid delivery particle of any one of claims 1- 100 or the system of claim 191 or 192; and (b) a pharmaceutically acceptable excipient.

194. A kit comprising (a) the lipid delivery particle of any one of claims 1-100, the system of claim 191 or 192, or the pharmaceutical composition of claim 193; and (b) an information material containing instructions for administering a dosage of the lipid delivery particle or the system, or a dosage form of the pharmaceutical composition to a subject.

195. A method of treating a disease or a condition in a subject in need thereof, comprising administering to the subject the lipid delivery particle of any one of claims 1-100, the system of claim 191 or 192, or the pharmaceutical composition of claim 193.

196. A method comprising contacting a cell with the lipid delivery particle of any one of claims 1-100.

197. A method comprising contacting a cell with the system of claim 191 or 192.

198. A method comprising administering the lipid delivery particle of any one of claims 1-100, the system of claim 191 or 192, or the pharmaceutical composition of claim 193 to a subject in need thereof.

199. A method of producing the lipid delivery particle of any one of claims 1-100.

200. The method of claim 199, comprising contacting a producer cell with the composition of any one of claims 185-190.

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