Pharmaceutical composition containing virus particles, and method of using the same.

Abstract

Pharmaceutical compositions containing viruses such as lentiviruses, including pseudotyped lentiviruses, and methods for using the same are provided herein. Methods for using the pharmaceutical compositions are also provided herein.

Description

[Technical Field]

[0001] Related applications This application claims the benefit of U.S. Provisional Application No. 63 / 492,664, filed on 28 March 2023, which is incorporated herein by reference in its entirety.

[0002] Reference to sequence listings filed electronically This application is filed electronically in XML format and includes a sequence listing which is incorporated in its entirety herein by reference. The XML copy was created on 11 March 2024, is named "INH-025WO_SL", and is 97,721 bytes in size.

[0003] The embodiments provided herein relate to viral vectors and pharmaceutical compositions containing them. [Background technology]

[0004] The physical and functional stabilization of purified lentiviral particles requires an optimal formulation composition. To ensure optimal shelf life, pH, ionic strength, and salt concentration, as well as stabilizing excipients during processing, freezing, thawing, handling, and storage, must be considered. Lentiviral vectors have previously been formulated primarily for ex vivo use, involving a single freeze-thaw cycle. The development of lentiviral vectors for direct in vivo administration, requiring two freeze-thaw cycles, necessitates a formulation that stabilizes the product throughout this process. This is important because in vivo administration requires the use of appropriate formulation excipients that are safe for human administration and have optimal pH and osmotic pressure to minimize viral particle aggregation while maintaining functional titer. The pharmaceutical composition containing viral particles must have a higher ionic strength to minimize viral particle aggregation and must include stabilizing excipients to maintain the functional titer of the viral particles throughout multiple freeze-thaw cycles and potential retention times during processing, after thawing, and before dose administration. This disclosure addresses those and other needs. [Overview of the project]

[0005] The disclosed embodiments specifically relate to a viral vector containing a VSV-G polypeptide, and a pharmaceutical composition containing a VSV-G specific virus and its particles.

[0006] In some embodiments, a pharmaceutical composition is provided comprising a lentiviral vector, a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 100 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 800 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0007] In some embodiments, the lentiviral vector is approximately 1.0E +05 ~Approximately 1.0E +09 It exists at a concentration of transduction units (TU) / mL.

[0008] In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer.

[0009] In some embodiments, the histidine buffer is present at a concentration of approximately 10 mM to approximately 30 mM.

[0010] In some embodiments, the pharmaceutical composition has a pH of about 6.5 to about 7.5.

[0011] In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 7.0.

[0012] In some embodiments, the pharmaceutically acceptable salt is sodium chloride.

[0013] In some embodiments, sodium chloride is present at a concentration of approximately 150 mM.

[0014] In some embodiments, the sugar is sucrose.

[0015] In some embodiments, sucrose is present at approximately 4% (w / v).

[0016] In some embodiments, the protein excipient is non-recombinant human serum albumin. 。

[0017] In some embodiments, non-recombinant human serum albumin is present at approximately 1% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.5% (w / v).

[0018] In some embodiments, the lentiviral vector is a VSV-G pseudotyped lentivirus.

[0019] In some embodiments, the VSV-G pseudotyped lentivirus is approximately 1.0E +05 ~Approximately 1.0E +09 It exists at a concentration of TU / mL.

[0020] In some embodiments, the VSV-G pseudotyped lentivirus comprises a VSV-G polypeptide containing a mutation corresponding to the mutation at position 182 of SEQ ID NO: 2.

[0021] In some embodiments, a pharmaceutical composition is provided, comprising VSV-G pseudotyped lentivirus, about 10 mM to about 30 mM L-histidine buffer, about 100 mM to about 200 mM sodium chloride, about 1% (w / v) to about 5% (w / v) sucrose, and about 0.1% (w / v) to about 2% (w / v) unrecombinant human serum albumin, wherein the pharmaceutical composition has a pH of about 5.5 to about 8.0. In some embodiments, the plant-recombinant human serum albumin is Exbumin®.

[0022] In some embodiments, the VSV-G pseudotyped lentivirus is approximately 1.0E +05 ~Approximately 1.0E +09 It exists at a concentration of TU / mL.

[0023] In some embodiments, L-histidine is present at a concentration of about 20 mM, and the pharmaceutical composition has a pH of about 7.0.

[0024] In some embodiments, sodium chloride is present at a concentration of approximately 150 mM.

[0025] In some embodiments, sucrose is present at approximately 4% (w / v).

[0026] In some embodiments, non-recombinant human serum albumin is present at approximately 0.5% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1% (w / v).

[0027] In some embodiments, the VSV-G pseudotyped lentivirus comprises a VSV-G polypeptide containing a mutation corresponding to the mutation at position 182 of SEQ ID NO: 2.

[0028] In some embodiments, the VSV-G polypeptide contains mutations corresponding to I182A, I182D, or I182E compared to the sequence of SEQ ID NO: 2.

[0029] In some embodiments, the polypeptide includes the T214N and / or T352A mutation.

[0030] In some embodiments, the polypeptide includes substitutions at positions I182, T214, and T352 of SEQ ID NO: 2.

[0031] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G polypeptide containing mutations corresponding to the mutations at positions 182, 214, and / or 352 of SEQ ID NO: 2, an L-histidine buffer at a concentration of about 10 mM to about 30 mM, sodium chloride at a concentration of about 100 mM to about 200 mM, sucrose in an amount of about 1% (w / v) to about 5% (w / v), and unrecombinant human serum albumin in an amount of about 0.1% (w / v) to about 2% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5. [Brief explanation of the drawing]

[0032] [Figure 1] This document describes lentiviral vector processes for ex vivo and in vivo use. [Figure 2] This shows the screening of VSVG-LV formulations. [Figure 3] This study demonstrates the development of a formulation suitable for intravenous and intralymphatic administration by stabilizing the LV through two freeze-thaw cycles. [Figure 4] This document presents a formulation confirmation study demonstrating the selection of histidine buffer. [Figure 5A] This shows the optimal [NaCl] concentration that helps minimize LV particle aggregation without affecting LV stability. It also shows the effect of [NaCl] on particle size distribution. [Figure 5B] This study shows the optimal [NaCl] level to minimize LV particle aggregation without affecting LV stability. It also demonstrates the effect of [NaCl] on viral titer using fresh and 1×F / T samples. [Figure 6A] The results of the HSS formulation optimization study are presented. Better formulation stability was observed using 1% Exbumin. [Figure 6B] The results of the HSS formulation optimization study are presented. The effect of [NaCl] on particle size distribution in the absence of Exbumin is shown. [Figure 6C] The results of the HSS formulation optimization study are shown. The effect of [NaCl] on particle size distribution in the presence of 1% Exbumin is shown. [Figure 6D]The results of the HSS formulation optimization study are presented. The effect of pH on the particle size distribution of 150 mM NaCl and 1% Exbumin formulations is shown. [Figure 7A] This document compares the stability of formulations containing recombinant HSA (Exbumin®) and non-recombinant HSA. The results are presented after three freeze-thaw cycles and 20-hour incubations at various temperatures. [Figure 7B] This document compares the stability of formulations containing recombinant HSA (Exbumin®) and non-recombinant HSA. The results are presented after three freeze-thaw cycles and 72-hour incubation at various temperatures. [Figure 8A] The crystal structure of VSV-G bound to LDL-R is shown. The crystal structure of VSV-G bound to CR3 of LDL-R is shown. [Figure 8B] The crystal structure of VSV-G bound to LDL-R is shown. The crystal structure of VSV-G bound to CR2 of LDL-R is shown. [Figure 9A] This study demonstrates the effect of adding electrolytic amino acids to the VSV-G:LDL-R binding interface on intrinsic tropism and fusion properties. It also shows the titration of VSV-G constructs on SupT1 cells. [Figure 9B] The effects of adding electrolytic amino acids to the VSV-G:LDL-R binding interface on intrinsic tropism and fusion properties are shown. The functional titers of each construct calculated from the titration in Figure 9A are shown. [Figure 10A] The alignments of the ectodomains of different VSV-G proteins from different strains are shown. 10A, 10B, 10C, 10D, and 10E are portions from the same alignment, each divided into separate figures for easier visualization. [Figure 10B] The alignments of the ectodomains of different VSV-G proteins from different strains are shown. 10A, 10B, 10C, 10D, and 10E are portions from the same alignment, each divided into separate figures for easier visualization. [Figure 10C]The alignments of the ectodomains of different VSV-G proteins from different strains are shown. 10A, 10B, 10C, 10D, and 10E are portions from the same alignment, each divided into separate figures for easier visualization. [Figure 10D] The alignments of the ectodomains of different VSV-G proteins from different strains are shown. 10A, 10B, 10C, 10D, and 10E are portions from the same alignment, each divided into separate figures for easier visualization. [Figure 10E] The alignments of the ectodomains of different VSV-G proteins from different strains are shown. 10A, 10B, 10C, 10D, and 10E are portions from the same alignment, each divided into separate figures for easier visualization. [Modes for carrying out the invention]

[0033] The embodiments described herein are not limited to any specific formulations, compositions, and experimental conditions disclosed, as such formulations, compositions, and experimental conditions may vary. It should also be understood that the terminology used herein is intended solely to describe and not to limit any particular embodiment.

[0034] Furthermore, the formulations, compositions, and experimental conditions described herein utilize conventional molecular and cell biological and immunological techniques known to those skilled in the art, unless otherwise indicated. Such techniques are well known to those skilled in the art and are adequately described in the literature. See, for example, Ausubel, et al., ed., Current Protocols in Molecular Biology, John Wiley & Sons, Inc., NY, NY (1987-2008), including all appendices; Molecular Cloning: A Laboratory Manual (Fourth Edition) by MR. Green and J. Sambrook; and Harlow et al., Antibodies: A Laboratory Manual, Chapter 14, Cold Spring Harbor Laboratory, Cold Spring Harbor (2013, 2nd edition).

[0035] Unless otherwise specified, scientific and technical terms used herein have meanings that are generally understood by those skilled in the art. Where any ambiguity may exist, the definitions provided herein shall prevail over any dictionary or external definitions. Unless the context specifically requires otherwise, singular terms shall include plural forms, and plural terms shall include singular forms. The use of "or" means "and / or" unless otherwise specified. The use of the term "including" and its other conjugations (e.g., "includes" and "included") means non-limiting.

[0036] In general, the terms used herein in relation to cell and tissue culture, molecular biology, immunology, microbiology, genetics, and protein and nucleic acid chemistry, as well as hybridization, are well-known and commonly used in the art. Unless otherwise indicated, the methods and techniques described herein are generally carried out in accordance with common practices well known in the art, and as described in the various general and more specific references cited and indicated throughout this specification. Enzyme reactions are carried out in accordance with the manufacturer's specifications, as commonly carried out in the art, or as described herein. The terms used herein in relation to analytical chemistry, synthetic organic chemistry, and medicinal chemistry and pharmaceutical chemistry, as well as the experimental procedures and techniques thereto, are well-known and commonly used in the art.

[0037] Unless otherwise specified in the context, singular terms shall include the plural form, and plural terms shall include the singular form.

[0038] To facilitate understanding of this disclosure, certain terms are defined below.

[0039] As used herein, the terms "a" or "an" mean "at least one" or "one or more" unless the context clearly indicates otherwise.

[0040] Where used herein, the term “about” means that the numerical value is an approximation and that small variations will not significantly affect the implementation of the disclosed embodiment. Where numerical limitations are used, unless otherwise indicated by the context, “about” means that a ±10% variation in the numerical value will remain within the scope of the disclosed embodiment. Furthermore, where the phrase “about x to y” is written, the term “about” can be used interchangeably with the phrase “about x to y” unless both x and y are modified to indicate a different context.

[0041] As used herein, the terms “individual,” “subject,” or “patient” are used synonymously and mean any animal, including mice, rats and other rodents, rabbits, dogs, cats, pigs, cattle, sheep, horses, or primates such as humans.

[0042] As used herein, the terms “comprising” (and any conjugations of “comprising,” such as “comprise,” “comprises,” and “comprised,” “having” (and any conjugations of “having,” such as “have,” and “has,” “has,” “having,” “having,” “having,” “having,” “having,” “having,” “having,” “having,” and any conjugations of “having,” such as “havings,” and “having,” “having,” or “having,” “having,” are open or non-restrictive and do not exclude any additional elements or steps of method not described herein. Any step or composition using the transitional phrase “comprise” or “comprising” may also be said to describe the same thing as using the transitional phrase “consisting of” or “consists.”

[0043] As used herein, the term "viral vector recovery rate" is defined as the amount of viral vector after filtration relative to the amount of viral vector before filtration, expressed as a percentage.

[0044] As used herein, the term "purified viral vector" is defined as a viral vector purified from a cell culture sample using at least one chromatographic step.

[0045] As used herein, a “non-concentrated” viral vector is a viral vector in a solution that has not undergone a concentration step during its preparation. As used herein, a “non-concentrated” viral vector is not limited to the concentration of viral particles within it, but rather simply indicates whether or not the solution containing the viral vector has undergone a concentration step, unless otherwise explicitly stated.

[0046] As used herein, the term “contact” means bringing two elements together in an in vitro or in vivo system. For example, “contact” a virus or vector described herein with an individual, patient, or cells includes administering the virus to an individual or patient, such as a human, and introducing a compound into a sample, for example, a cell preparation or purified preparation containing cells.

[0047] As used herein, the terms “fused” or “linked” as used with respect to proteins having different domains or heterologous sequences mean that such protein domains are connected to each other by either peptide bonds or other covalent bonds and become part of the same peptide chain. Domains or sections may be directly linked or fused to each other, or another domain or peptide sequence may be between the two domains or sequences, and such sequences are still considered fused or linked to each other. In some embodiments, the various domains or proteins provided herein may be directly linked or fused to each other, or a linker sequence, such as the glycine / serine sequence described herein, may link the two domains together.

[0048] An animal's "disease" refers to a health condition in which the animal cannot maintain homeostasis, and if the disease is not improved, the animal's health will continue to deteriorate. On the other hand, an animal's "disability" refers to a health condition in which the animal can maintain homeostasis, but which is less desirable than when there is no disability. Leaving a disability untreated does not necessarily lead to a further decline in the animal's health.

[0049] "Effective dose" or "therapeutic effective dose" is used synonymously herein and refers to the amount of a compound, formulation, substance, or composition described herein that is effective in achieving a particular biological outcome or in producing a therapeutic or preventive effect. Such an outcome may include, but is not limited to, administering an amount of the composition to a mammal that produces a detectable level of immune cell activation compared to immune cell activation detected in the absence of the composition. The immune response can be readily assessed by a number of methods known in the art. Those skilled in the art will understand that the amount of composition administered herein varies and can be readily determined based on several factors, such as the disease or condition being treated, the age, health status, and physical condition of the mammal being treated, the severity of the disease, and the specific compound being administered.

[0050] "Code" refers to the inherent property of a particular sequence of nucleotides in a polynucleotide (e.g., a gene, cDNA, or mRNA) to function as a template for the synthesis of other polymers and macromolecules having either a specific sequence of nucleotides (i.e., rRNA, tRNA, and mRNA) or a specific sequence of amino acids in a biological process, as well as the biological properties derived therefrom. Thus, a gene codes for a protein when a protein is produced in a cell or other biological system by the transcription and translation of mRNA corresponding to a gene. Both the coding strand (whose nucleotide sequence is identical to the mRNA sequence and is usually shown in a sequence listing) and the non-coding strand (used as a template for the transcription of a gene or cDNA) can be referred to as encoding a protein or other product of the gene or cDNA.

[0051] An "expression vector" refers to a vector containing a recombinant polynucleotide, the recombinant polynucleotide containing an expression regulatory sequence operably ligated to the nucleotide sequence to be expressed. The expression vector contains sufficient cis-acting elements for expression. Other elements for expression can be supplied by host cells or in an in vitro expression system. Expression vectors include all known in the art, such as cosmids, plasmids (e.g., naked or liposome-containing) and viruses (e.g., Sendai virus, lentivirus, retrovirus, adenovirus, and adeno-associated virus) incorporating recombinant polynucleotides.

[0052] As used herein, the term “ex vivo” with respect to cells transfected, transfected, or transformed ex vivo means cells transfected, transfected, or transformed outside of the subject, i.e., cells removed from the subject before such cells are transfected, transfected, or transformed.

[0053] As used herein, “identity” refers to the identity of subunit sequences between two nucleic acid molecules or amino acid molecules, or between two polymer molecules, such as two polynucleotide molecules or polypeptide molecules. Two amino acid sequences are identical at the same position if, for example, the position in each of two polypeptide molecules is occupied by arginine. The identity or degree to which two amino acids or two nucleic acid sequences have the same residue at the same position in their alignment is often expressed as a percentage. The identity between two amino acid sequences or two nucleic acid sequences depends directly on the number of matching or identical positions; for example, if half of the positions of the two sequences are identical, the two sequences are 50% identical, and if 90% of the positions (e.g., 9 out of 10) match or are identical, the two amino acid sequences are 90% identical.

[0054] "Substantially identical" means that a polypeptide or nucleic acid molecule exhibits at least 50% identity with respect to a reference amino acid sequence (e.g., any one of the amino acid sequences described herein) or nucleic acid sequence (e.g., any one of the nucleic acid sequences described herein). In some embodiments, such sequences are at least 60%, 80%, or 85%, or 90%, 95%, or even 99%, identical at the amino acid level or nucleic acid level to the sequence used for comparison. Other identity percentages for specific sequences are described herein.

[0055] Sequence identity can be measured / determined using sequence analysis software (e.g., Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis. 53705, BLAST, BESTFIT, GAP, or PILEUP / PRETTYBOX programs). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conservative substitutions typically include intragroup substitutions of glycine and alanine, valine, isoleucine, and leucine, aspartic acid, glutamic acid, asparagine, and glutamine, serine and threonine, lysine and arginine, and phenylalanine and tyrosine. An exemplary method for determining the degree of identity is to use the BLAST program, which indicates closely related sequences with probability scores from e3 to e100. In some embodiments, sequence identity is determined using BLAST with default settings.

[0056] To the extent that the embodiments described herein encompass compositions containing various proteins, such proteins may contain amino acid sequences having sequence identity with respect to the amino acid sequences disclosed herein. Therefore, in certain embodiments, depending on the specific sequence, the degree of sequence identity is preferably greater than 50% with respect to the SEQ ID NOs disclosed herein (e.g., 60%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more). In addition to these percentages, other identity percentages are also indicated herein. Polypeptide identity can be determined by the Smith-Waterman homology search algorithm implemented in the MPSRCH program (Oxford Molecular) using affine gap search with a parameter gap-open penalty of -12 and a gap-elongation penalty of 1. Such proteins contain one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) conserved amino acid substitutions (i.e., one amino acid being replaced by another amino acid with a congenerate side chain) compared to the proteins of this disclosure. Genetically encoded amino acids are generally classified into four families: (1) acidic, i.e., aspartic acid, glutamic acid; (2) basic, i.e., lysine, arginine, histidine; (3) nonpolar, i.e., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan; and (4) non-charged, i.e., glycine, asparagine, glutamine, cysteine, serine, threonine, tyrosine. Phenylalanine, tryptophan, and tyrosine are sometimes classified together as aromatic amino acids. Typically, single amino acid substitutions within these families do not significantly affect biological activity. The protein may have one or more single amino acid deletions (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) compared to the disclosed protein sequence. The protein may also have one or more insertions (e.g., each of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) (e.g., each of 1, 2, 3, 4, or 5 amino acids) compared to the disclosed protein sequence.

[0057] As used herein, the term "in vivo" with respect to cells transfected, transformed, or otherwise transfected in vivo means that the cells are transfected, transformed, or otherwise transfected within the subject, and that the cells have not been removed from the subject before being transfected, transfected, or transformed.

[0058] "Isolated" means modified or removed from its natural state. For example, nucleic acids or peptides that naturally exist in living animals are not "isolated," but the same nucleic acids or peptides are "isolated" if they are partially or completely separated from coexisting substances in their natural state. Isolated nucleic acids or proteins may exist in a substantially purified form or in an environment that is not their original environment, such as a host cell.

[0059] As used herein, "lentivirus" refers to a genus of the family Retroviridae that can infect non-dividing cells. Non-exclusive examples of lentiviruses include HIV, SIV, and FIV. Lentivirus-derived vectors or virus-like particles can be used to transduce cells to deliver genes or other molecules for expression in vitro, ex vivo, or in vivo within cells.

[0060] The term "modified," as used herein, means an altered state or structure of a molecule or cell provided herein. Molecules can be modified in many ways, including chemical, structural, and functional modifications such as mutation, substitution, insertion, or deletion (e.g., internal deletion cleavage). Cells can be modified by the introduction of nucleic acids or the expression of heterologous proteins.

[0061] As used herein, the term “modulation” means mediating an increase or decrease in the response level of a subject compared to the response level of the subject in the absence of the treatment or compound, and / or compared to the response level of an otherwise identical but untreated subject. This term encompasses disruption and / or influence of the original signal or response, thereby mediating a beneficial therapeutic response in a subject such as a human.

[0062] Unless otherwise specified, "nucleotide sequences encoding an amino acid sequence" includes all nucleotide sequences that are degenerate and encode the same amino acid sequence. The phrase "nucleotide sequence encoding a protein or RNA" may include introns to the extent that a nucleotide sequence encoding a protein may contain introns in several versions.

[0063] The term "oligonucleotide" typically refers to a short polynucleotide. Naturally, when a nucleotide sequence is represented by a DNA sequence (i.e., A, T, C, G), this also refers to the corresponding RNA sequence (i.e., A, U, C, G) where "T" is replaced by "U".

[0064] Parenteral administration of the composition includes, for example, subcutaneous (sc), intravenous (iv), intramuscular (im), or intracapsular injection, subarachnoid, or infusion techniques.

[0065] As used herein, the term “polynucleotide” is defined as a chain of nucleotides. Furthermore, nucleic acids are polymers of nucleotides. Therefore, as used herein, the terms “nucleic acid” and “polynucleotide” are interchangeable. As used herein, polynucleotides include, but are not limited to, all nucleic acid sequences obtained by any method available in the art, including, but not limited to, recombinant methods such as cloning techniques and PCR, and cloning of nucleic acid sequences from recombinant libraries or cell genomes.

[0066] As used herein, the terms “peptide,” “polypeptide,” and “protein” are used synonymously and refer to compounds composed of multiple amino acid residues covalently linked by peptide bonds. As used herein, this term refers to both short-chain (e.g., commonly referred to in the art as peptides, oligopeptides, and oligomers) and long-chain (commonly referred to in the art as proteins), of which there are many types. Polypeptides include, among other things, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, polypeptide variants, modified polypeptides, derivatives, analogs, and fusion proteins. Polypeptides include native peptides, recombinant peptides, synthetic peptides, or combinations thereof.

[0067] The terms “pseudotype” or “pseudotyped viral particle,” as used herein, refer to viral particles having glycoproteins derived from another virus that has a viral vector encoding an envelope or envelope glycoprotein from a virus different from the parent virus. Thus, the host range of the vector particle can be extended or modified depending on the type of cell surface receptor used by the glycoprotein. For example, viruses can be pseudotyped using the VSV-G mutant protein provided herein.

[0068] Where used herein in relation to antibodies, the term “specifically binds” means that an antibody recognizes a particular antigen but substantially does not recognize or bind to other molecules in the sample. For example, an antibody that specifically binds to an antigen from one species may also bind to that antigen from one or more species. However, such interspecies reactivity itself does not change the classification of the antibody as specific. In another example, an antibody that specifically binds to an antigen may also bind to different alleles of the antigen. However, such cross-reactivity itself does not change the classification of the antibody as specific. In some cases, the terms “specific binding” or “specifically binding” can be used in relation to the interaction of an antibody, protein, or peptide with a second chemical species, meaning that the interaction depends on the presence of a specific structure on the chemical species (e.g., an antigenic determinant or epitope) (e.g., an antibody recognizes and binds to a specific protein structure, rather than to proteins in general). If an antibody is specific to epitope “A”, then in a reaction involving labeled “A” and the antibody, the presence of a molecule containing epitope A (or unlabeled free A) will reduce the amount of labeled A that binds to the antibody. In some embodiments, the target-directed moieties described herein can be used to target viral particles containing a variant VSV-G protein or viral particles containing other viral structural proteins used to pseudotype the virus, and such target-directed moieties can specifically bind to their target.

[0069] As used herein, “therapeutic” means treatment and / or prevention. Therapeutic effects are obtained by suppression, remission, or eradication of the disease.

[0070] As used herein, the terms “transfected,” “transformed,” or “transduced” refer to the process by which an exogenous nucleic acid is transferred to or introduced into a cell. A “transfected,” “transformed,” or “transduced” cell is a cell that has been transfected, transformed, or transduced with an exogenous nucleic acid. Such cells include primary target cells and their offspring. In some embodiments, transfection, transformation, or transduction is performed or occurs in vivo.

[0071] A "vector" is a composition containing isolated nucleic acids that encode a protein or peptide. Numerous vectors are known in the art, including, but not limited to, linear polynucleotides, plasmids, DNA, and RNA. Examples of viral vectors include, but are not limited to, Sendai virus vectors, adenovirus vectors, adeno-associated virus vectors, retrovirus vectors, and lentiviral vectors.

[0072] As used herein, the terms “viral vector,” “virus,” and “viral particle” are understood to be synonymous unless the context of the embodiment specifically or expressly indicates otherwise. This understanding also applies to specific viral vectors. For example, as used herein, the terms “lentiviral vector,” “lentivirus,” and “lentiviral particle” are understood to be synonymous unless the context of the embodiment specifically or expressly indicates otherwise.

[0073] A "carrier" or "delivery vehicle" may include viral particles, viruses, polylysine compounds, and liposomes, which facilitate the transfer of nucleic acids into cells. Proteins or peptides can also be delivered to cells using carriers or delivery vehicles.

[0074] Scope: Through this disclosure, various aspects of the embodiments can be expressed in the form of a scope. Naturally, descriptions in the form of a scope are merely for convenience and brevity and should not be interpreted as inflexible limitations. Therefore, a scope description should be considered to specifically disclose all possible partial scopes and the individual numerical values ​​within those scopes. For example, a scope description such as 1 to 6 should be considered to have specifically disclosed partial scopes such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, and the individual numerical values ​​within those scopes, e.g., 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the width of the scope. Unless otherwise expressly stated, the disclosed scope includes the endpoints of that scope.

[0075] Pharmaceutical composition As used herein, the term "composition" means a product resulting from a mixture or combination of two or more elements or components.

[0076] As used herein, the term “carrier” encompasses carriers, excipients, and diluents, meaning materials, compositions, or vehicles such as liquid or solid fillers, diluents, excipients, solvents, or encapsulating materials that are involved in carrying or transporting pharmaceutical, cosmetic, or other agents across tissue layers.

[0077] The term "pharmaceutically acceptable" is used herein to mean an agent / compound, salt, composition, pharmaceutical dosage form, etc., of interest that is suitable for use in contact with human and / or other mammalian tissues within the bounds of appropriate medical judgment, and that is commensurate with a reasonable benefit / risk ratio without causing excessive toxicity, irritation, allergic response, or other problems or complications. In some embodiments, pharmaceutically acceptable means that it is approved by a federal or state regulatory authority, or is listed in the United States Pharmacopeia or other generally accepted pharmacopoeia for use in animals (e.g., mammals), more specifically in humans.

[0078] As used herein, "stable", "stable composition", or "stable pharmaceutical composition" refers to a composition or pharmaceutical composition that maintains the characteristics of the composition within a defined range when exposed to various stress factors such as heat, light, temperature, humidity, repeated freeze-thaw cycles, and long-term storage, but not limited thereto. Such characteristics include, but are not limited to, pH, presence of aggregates, functional titer, or concentration of protein excipients. In some embodiments, the defined ranges for pH, presence of aggregates, functional titer, or concentration of protein excipients are as provided herein.

[0079] The term "excipient" refers to a pharmacologically inactive substance formulated with an antibody, antigen-binding fragment thereof, viral vector, or any other pharmacologically active molecule provided herein.

[0080] In some embodiments, provided is a pharmaceutical composition comprising a lentiviral vector, a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 100 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 800 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), and the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0081] In some embodiments, the pharmaceutical composition +05 ~ about 1.0E +09 contains a lentiviral vector at a concentration of TU / mL.

[0082] In some embodiments, the lentiviral vector is about 1.0E +05 ~ about 1.0E +09 TU / mL, about 1.0E +05 ~ about 1.0E +08 TU / mL, about 1.0E +05 ~ about 1.0E +07 TU / mL, about 1.0E +05 ~ 1.0E +06 TU / mL, about 1.0E +06 ~ about 1.0E+09 TU / mL, approximately 1.0E +06 ~Approximately 1.0E +08 TU / mL, approximately 1.0E +06 ~Approximately 1.0E +07 TU / mL, approximately 1.0E +07 ~Approximately 1.0E +09 TU / mL, approximately 1.0E +07 ~Approximately 1.0E +08 TU / mL, or approximately 1.0E +08 ~Approximately 1.0E +09 It exists at a concentration of TU / mL.

[0083] In some embodiments, the lentiviral vector is approximately 1.0E +05 ~Approximately 1.0E +09 It is present at a concentration of TU / mL. In some embodiments, the lentiviral vector is approximately 1.0E +05 ~Approximately 1.0E +08 It is present at a concentration of TU / mL. In some embodiments, the lentiviral vector is approximately 1.0E +05 ~Approximately 1.0E +07 It is present at a concentration of TU / mL. In some embodiments, the lentiviral vector is approximately 1.0E +05 ~Approximately 1.0E +06 It is present at a concentration of TU / mL. In some embodiments, the lentiviral vector is approximately 1.0E +06 ~Approximately 1.0E +09 It is present at a concentration of TU / mL. In some embodiments, the lentiviral vector is approximately 1.0E +06 ~Approximately 1.0E +08 It is present at a concentration of TU / mL. In some embodiments, the lentiviral vector is approximately 1.0E +06 ~Approximately 1.0E +07 It is present at a concentration of TU / mL. In some embodiments, the lentiviral vector is approximately 1.0E +07 ~Approximately 1.0E +09 It is present at a concentration of TU / mL. In some embodiments, the lentiviral vector is approximately 1.0E +07 ~Approximately 1.0E +08 It is present at a concentration of TU / mL. In some embodiments, the lentiviral vector is approximately 1.0E+08 ~Approximately 1.0E +09 It exists at a concentration of TU / mL.

[0084] In some embodiments, the lentiviral vector is at least 1.0E +05 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 2.0E +05 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 3.0E +05 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 4.0E +05 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 5.0E +05 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 6.0E +05 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 7.0E +05 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 8.0E +05 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 9.0E +05 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 1.0E +06 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 2.0E +06 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 3.0E +06 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 4.0E +06 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 5.0E +06 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 6.0E +06 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 7.0E +06It is present at a concentration of . In some embodiments, the lentiviral vector is at least 8.0E +06 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 9.0E +06 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 1.0E +07 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 2.0E +07 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 3.0E +07 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 4.0E +07 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 5.0E +07 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 6.0E +07 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 7.0E +07 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 8.0E +07 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 9.0E +07 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 1.0E +08 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 2.0E +08 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 3.0E +08 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 4.0E +08 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 5.0E +08 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 6.0E +08 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 7.0E+08 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 8.0E +08 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 9.0E +08 It is present at a concentration of . In some embodiments, the lentiviral vector is at least 1.0E +09 It exists at this concentration.

[0085] In some embodiments, pharmaceutically acceptable buffers are approximately 5 mM to 100 mM, approximately 5 mM to 90 mM, approximately 5 mM to 80 mM, approximately 5 mM to 70 mM, approximately 5 mM to 60 mM, approximately 5 mM to 50 mM, approximately 5 mM to 40 mM, approximately 5 mM to 30 mM, approximately 5 mM to 25 mM, approximately 10 mM to 100 mM, approximately 10 mM to 90 mM, approximately 10 mM to 80 mM, approximately 10 mM to 70 mM, and approximately 1 It has concentrations of 0 mM to approximately 60 mM, approximately 10 mM to approximately 50 mM, approximately 10 mM to approximately 40 mM, approximately 10 mM to approximately 30 mM, approximately 10 mM to approximately 25 mM, approximately 15 mM to approximately 100 mM, approximately 15 mM to approximately 90 mM, approximately 15 mM to approximately 80 mM, approximately 15 mM to approximately 70 mM, approximately 15 mM to approximately 60 mM, approximately 15 mM to approximately 50 mM, approximately 15 mM to approximately 40 mM, approximately 15 mM to approximately 30 mM, or approximately 15 mM to approximately 25 mM.

[0086] In some embodiments, the pharmaceutically acceptable buffer has concentrations of approximately 5 mM to approximately 100 mM, approximately 5 mM to approximately 70 mM, approximately 5 mM to approximately 60 mM, approximately 10 mM to approximately 60 mM, approximately 10 mM to approximately 50 mM, approximately 10 mM to approximately 40 mM, approximately 15 mM to approximately 30 mM, or approximately 15 mM to approximately 25 mM.

[0087] In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 5 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 10 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 15 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 20 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 25 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 30 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 35 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 40 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 45 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 50 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 55 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 60 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 65 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 70 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 75 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 80 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 85 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 90 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 95 mM. In some embodiments, the pharmaceutically acceptable buffer has a concentration of about 100 mM.

[0088] In some embodiments, pharmaceutically acceptable buffers are selected from histidine buffer, HEPES, phosphate buffer, citrate buffer, acetate buffer, succinate buffer, phosphate buffer, acetate buffer, citrate buffer, succinate buffer, ascorbic acid buffer, glutamate buffer, lactate buffer, maleate buffer, trometamol buffer, or gluconate buffer, or any combination thereof.

[0089] In some embodiments, the pharmaceutically acceptable buffer is histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is HEPES. In some embodiments, the pharmaceutically acceptable buffer is phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is ascorbic acid buffer. In some embodiments, the pharmaceutically acceptable buffer is glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is lactate buffer. In some embodiments, the pharmaceutically acceptable buffer is maleate buffer. In some embodiments, the pharmaceutically acceptable buffer is trometamol buffer. In some embodiments, the pharmaceutically acceptable buffer is gluconate buffer.

[0090] In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer.

[0091] In some embodiments, the histidine buffer is available in concentrations of approximately 5 mM to 100 mM, 5 mM to 90 mM, 5 mM to 80 mM, 5 mM to 70 mM, 5 mM to 60 mM, 5 mM to 50 mM, 5 mM to 40 mM, 5 mM to 30 mM, 5 mM to 25 mM, 10 mM to 100 mM, 10 mM to 90 mM, 10 mM to 80 mM, 10 mM to 70 mM, and 10 mM It has concentrations of approximately 60mM, 10mM to 50mM, 10mM to 40mM, 10mM to 30mM, 10mM to 25mM, 15mM to 100mM, 15mM to 90mM, 15mM to 80mM, 15mM to 70mM, 15mM to 60mM, 15mM to 50mM, 15mM to 40mM, 15mM to 30mM, or 15mM to 25mM.

[0092] In some embodiments, the histidine buffer has concentrations of approximately 5 mM to 100 mM, approximately 5 mM to 70 mM, approximately 5 mM to 60 mM, approximately 10 mM to 60 mM, approximately 10 mM to 50 mM, approximately 10 mM to 40 mM, approximately 15 mM to 30 mM, or approximately 15 mM to 25 mM.

[0093] In some embodiments, the histidine buffer has a concentration of about 5 mM. In some embodiments, the histidine buffer has a concentration of about 10 mM. In some embodiments, the histidine buffer has a concentration of about 11 mM. In some embodiments, the histidine buffer has a concentration of about 12 mM. In some embodiments, the histidine buffer has a concentration of about 13 mM. In some embodiments, the histidine buffer has a concentration of about 14 mM. In some embodiments, the histidine buffer has a concentration of about 15 mM. In some embodiments, the histidine buffer has a concentration of about 16 mM. In some embodiments, the histidine buffer has a concentration of about 17 mM. In some embodiments, the histidine buffer has a concentration of about 18 mM. In some embodiments, the histidine buffer has a concentration of about 19 mM. In some embodiments, the histidine buffer has a concentration of about 20 mM. In some embodiments, the histidine buffer has a concentration of about 25 mM. In some embodiments, the histidine buffer has a concentration of about 30 mM. In some embodiments, the histidine buffer has a concentration of about 35 mM. In some embodiments, the histidine buffer has a concentration of about 40 mM. In some embodiments, the histidine buffer has a concentration of about 45 mM. In some embodiments, the histidine buffer has a concentration of about 50 mM. In some embodiments, the histidine buffer has a concentration of about 55 mM. In some embodiments, the histidine buffer has a concentration of about 60 mM. In some embodiments, the histidine buffer has a concentration of about 65 mM. In some embodiments, the histidine buffer has a concentration of about 70 mM. In some embodiments, the histidine buffer has a concentration of about 75 mM. In some embodiments, the histidine buffer has a concentration of about 80 mM. In some embodiments, the histidine buffer has a concentration of about 85 mM. In some embodiments, the histidine buffer has a concentration of about 90 mM. In some embodiments, the histidine buffer has a concentration of about 95 mM. In some embodiments, the histidine buffer has a concentration of about 100 mM.

[0094] In some embodiments, the histidine buffer has a concentration of about 14 mM. In some embodiments, the histidine buffer is present at a concentration of about 20 mM.

[0095] In some embodiments, the pharmaceutical composition has a pH of about 6 to about 8, about 6.5 to about 8, about 7 to about 8, about 7.5 to about 8, about 6 to about 7.5, about 6 to about 7, about 6 to about 6.5, about 6.5 to about 7.5, or any value or range within those ranges. In some embodiments, the pharmaceutical composition has a pH of about 6.5 to about 7.5.

[0096] In some embodiments, the pharmaceutical composition has a pH of about 6.0. In some embodiments, the pharmaceutical composition has a pH of about 6.1. In some embodiments, the pharmaceutical composition has a pH of about 6.2. In some embodiments, the pharmaceutical composition has a pH of about 6.3. In some embodiments, the pharmaceutical composition has a pH of about 6.4. In some embodiments, the pharmaceutical composition has a pH of about 6.5. In some embodiments, the pharmaceutical composition has a pH of about 6.6. In some embodiments, the pharmaceutical composition has a pH of about 6.7. In some embodiments, the pharmaceutical composition has a pH of about 6.8. In some embodiments, the pharmaceutical composition has a pH of about 6.9. In some embodiments, the pharmaceutical composition has a pH of about 7.0. In some embodiments, the pharmaceutical composition has a pH of about 7.1. In some embodiments, the pharmaceutical composition has a pH of about 7.2. In some embodiments, the pharmaceutical composition has a pH of about 7.3. In some embodiments, the pharmaceutical composition has a pH of about 7.4. In some embodiments, the pharmaceutical composition has a pH of about 7.5. In some embodiments, the pharmaceutical composition has a pH of about 7.6. In some embodiments, the pharmaceutical composition has a pH of about 7.7. In some embodiments, the pharmaceutical composition has a pH of about 7.8. In some embodiments, the pharmaceutical composition has a pH of about 7.9. In some embodiments, the pharmaceutical composition has a pH of about 8.0.

[0097] In some embodiments, the pharmaceutical composition has a pH of about 7.0.

[0098] In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 6 to about 8. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 6.5 to about 7.5.

[0099] In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 6.0. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 6.1. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 6.2. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 6.3. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 6.4. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 6.5. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 6.6. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 6.7. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 6.8. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 6.9. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 7.0. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 7.1. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 7.2. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 7.3. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 7.4. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of 7.5. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 7.6.In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 7.7. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 7.8. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 7.9. In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 8.0.

[0100] In some embodiments, the pharmaceutically acceptable buffer is a histidine buffer, and the pharmaceutical composition has a pH of about 7.0.

[0101] In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 100 mM to about 800 mM, or any value or range in between.

[0102] In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 100 mM to about 800 mM. In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 100 mM to about 700 mM. In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 100 mM to about 600 mM. In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 100 mM to about 500 mM. In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 100 mM to about 400 mM. In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 100 mM to about 300 mM. In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 100 mM to about 250 mM. In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 100 mM to about 200 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 100 mM to about 175 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 100 mM to about 150 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 100 mM to about 125 mM.

[0103] In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 100 mM to about 800 mM. In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 125 mM to about 800 mM. In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 150 mM to about 800 mM. In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 175 mM to about 800 mM. In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 200 mM to about 800 mM. In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 250 mM to about 800 mM. In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 300 mM to about 800 mM. In some embodiments, pharmaceutically acceptable salts are present at concentrations of about 350 mM to about 800 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 400 mM to about 800 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 500 mM to about 800 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 600 mM to about 800 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 700 mM to about 800 mM.

[0104] In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 100 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 110 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 120 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 130 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 140 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 150 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 160 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 170 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 180 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 190 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 200 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 210 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 220 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 230 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 240 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 250 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 260 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 270 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 280 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 290 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 300 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 310 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 320 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 330 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 340 mM.In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 350 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 360 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 370 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 380 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 390 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 400 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 410 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 420 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 430 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 440 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 450 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 460 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 470 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 480 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 490 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 500 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 510 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 520 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 530 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 540 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 550 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 560 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 570 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 580 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 590 mM.In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 600 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 610 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 620 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 630 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 640 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 650 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 660 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 670 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 680 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 690 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 700 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 710 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 720 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 730 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 740 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 750 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 760 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 770 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 780 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 790 mM. In some embodiments, the pharmaceutically acceptable salt is present at a concentration of about 800 mM.

[0105] In some embodiments, the pharmaceutically acceptable salt is any suitable pharmaceutically acceptable salt. The pharmaceutically acceptable salts are known in the art, and any such salt is within the scope of this disclosure. In some embodiments, the pharmaceutically acceptable salt is selected from sodium chloride, potassium chloride, magnesium chloride, calcium chloride, or a combination thereof.

[0106] In some embodiments, the pharmaceutically acceptable salt is sodium chloride. In some embodiments, the pharmaceutically acceptable salt is potassium chloride. In some embodiments, the pharmaceutically acceptable salt is magnesium chloride. In some embodiments, the pharmaceutically acceptable salt is calcium chloride.

[0107] In some embodiments, the pharmaceutically acceptable salt is sodium chloride.

[0108] In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 800 mM, or any value or range in between. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 700 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 600 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 500 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 300 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 250 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 200 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 175 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 150 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 125 mM.

[0109] In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 800 mM. In some embodiments, sodium chloride is present at a concentration of about 125 mM to about 800 mM. In some embodiments, sodium chloride is present at a concentration of about 150 mM to about 800 mM. In some embodiments, sodium chloride is present at a concentration of about 175 mM to about 800 mM. In some embodiments, sodium chloride is present at a concentration of about 200 mM to about 800 mM. In some embodiments, sodium chloride is present at a concentration of about 250 mM to about 800 mM. In some embodiments, sodium chloride is present at a concentration of about 300 mM to about 800 mM. In some embodiments, sodium chloride is present at a concentration of about 350 mM to about 800 mM. In some embodiments, sodium chloride is present at a concentration of about 400 mM to about 800 mM. In some embodiments, sodium chloride is present at a concentration of about 500 mM to about 800 mM. In some embodiments, sodium chloride is present at a concentration of about 600 mM to about 800 mM. In some embodiments, sodium chloride is present at a concentration of about 700 mM to about 800 mM.

[0110] In some embodiments, sodium chloride is present at a concentration of about 100 mM. In some embodiments, sodium chloride is present at a concentration of about 110 mM. In some embodiments, sodium chloride is present at a concentration of about 120 mM. In some embodiments, sodium chloride is present at a concentration of about 130 mM. In some embodiments, sodium chloride is present at a concentration of about 140 mM. In some embodiments, sodium chloride is present at a concentration of about 150 mM. In some embodiments, sodium chloride is present at a concentration of about 160 mM. In some embodiments, sodium chloride is present at a concentration of about 170 mM. In some embodiments, sodium chloride is present at a concentration of about 180 mM. In some embodiments, sodium chloride is present at a concentration of about 190 mM. In some embodiments, sodium chloride is present at a concentration of about 200 mM. In some embodiments, sodium chloride is present at a concentration of about 210 mM. In some embodiments, sodium chloride is present at a concentration of about 220 mM. In some embodiments, sodium chloride is present at a concentration of about 230 mM. In some embodiments, sodium chloride is present at a concentration of about 240 mM. In some embodiments, sodium chloride is present at a concentration of about 250 mM. In some embodiments, sodium chloride is present at a concentration of about 260 mM. In some embodiments, sodium chloride is present at a concentration of about 270 mM. In some embodiments, sodium chloride is present at a concentration of about 280 mM. In some embodiments, sodium chloride is present at a concentration of about 290 mM. In some embodiments, sodium chloride is present at a concentration of about 300 mM. In some embodiments, sodium chloride is present at a concentration of about 310 mM. In some embodiments, sodium chloride is present at a concentration of about 320 mM. In some embodiments, sodium chloride is present at a concentration of about 330 mM. In some embodiments, sodium chloride is present at a concentration of about 340 mM. In some embodiments, sodium chloride is present at a concentration of about 350 mM. In some embodiments, sodium chloride is present at a concentration of approximately 360 mM.In some embodiments, sodium chloride is present at a concentration of about 370 mM. In some embodiments, sodium chloride is present at a concentration of about 380 mM. In some embodiments, sodium chloride is present at a concentration of about 390 mM. In some embodiments, sodium chloride is present at a concentration of about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 410 mM. In some embodiments, sodium chloride is present at a concentration of about 420 mM. In some embodiments, sodium chloride is present at a concentration of about 430 mM. In some embodiments, sodium chloride is present at a concentration of about 440 mM. In some embodiments, sodium chloride is present at a concentration of about 450 mM. In some embodiments, sodium chloride is present at a concentration of about 460 mM. In some embodiments, sodium chloride is present at a concentration of about 470 mM. In some embodiments, sodium chloride is present at a concentration of about 480 mM. In some embodiments, sodium chloride is present at a concentration of about 490 mM. In some embodiments, sodium chloride is present at a concentration of about 500 mM. In some embodiments, sodium chloride is present at a concentration of about 510 mM. In some embodiments, sodium chloride is present at a concentration of about 520 mM. In some embodiments, sodium chloride is present at a concentration of about 530 mM. In some embodiments, sodium chloride is present at a concentration of about 540 mM. In some embodiments, sodium chloride is present at a concentration of about 550 mM. In some embodiments, sodium chloride is present at a concentration of about 560 mM. In some embodiments, sodium chloride is present at a concentration of about 570 mM. In some embodiments, sodium chloride is present at a concentration of about 580 mM. In some embodiments, sodium chloride is present at a concentration of about 590 mM. In some embodiments, sodium chloride is present at a concentration of about 600 mM. In some embodiments, sodium chloride is present at a concentration of about 610 mM. In some embodiments, sodium chloride is present at a concentration of about 620 mM. In some embodiments, sodium chloride is present at a concentration of approximately 630 mM.In some embodiments, sodium chloride is present at a concentration of about 640 mM. In some embodiments, sodium chloride is present at a concentration of about 650 mM. In some embodiments, sodium chloride is present at a concentration of about 660 mM. In some embodiments, sodium chloride is present at a concentration of about 670 mM. In some embodiments, sodium chloride is present at a concentration of about 680 mM. In some embodiments, sodium chloride is present at a concentration of about 690 mM. In some embodiments, sodium chloride is present at a concentration of about 700 mM. In some embodiments, sodium chloride is present at a concentration of about 710 mM. In some embodiments, sodium chloride is present at a concentration of about 720 mM. In some embodiments, sodium chloride is present at a concentration of about 730 mM. In some embodiments, sodium chloride is present at a concentration of about 740 mM. In some embodiments, sodium chloride is present at a concentration of about 750 mM. In some embodiments, sodium chloride is present at a concentration of about 760 mM. In some embodiments, sodium chloride is present at a concentration of about 770 mM. In some embodiments, sodium chloride is present at a concentration of about 780 mM. In some embodiments, sodium chloride is present at a concentration of about 790 mM. In some embodiments, sodium chloride is present at a concentration of about 800 mM.

[0111] In some embodiments, sodium chloride is present at a concentration of approximately 150 mM.

[0112] In some embodiments, the pharmaceutically acceptable salt is potassium chloride.

[0113] In some embodiments, potassium chloride is present at a concentration of about 100 mM to about 800 mM, or any value or range in between. In some embodiments, potassium chloride is present at a concentration of about 100 mM to about 700 mM. In some embodiments, potassium chloride is present at a concentration of about 100 mM to about 600 mM. In some embodiments, potassium chloride is present at a concentration of about 100 mM to about 500 mM. In some embodiments, potassium chloride is present at a concentration of about 100 mM to about 400 mM. In some embodiments, potassium chloride is present at a concentration of about 100 mM to about 300 mM. In some embodiments, potassium chloride is present at a concentration of about 100 mM to about 250 mM. In some embodiments, potassium chloride is present at a concentration of about 100 mM to about 200 mM. In some embodiments, potassium chloride is present at a concentration of about 100 mM to about 175 mM. In some embodiments, potassium chloride is present at a concentration of about 100 mM to about 150 mM. In some embodiments, potassium chloride is present at a concentration of about 100 mM to about 125 mM.

[0114] In some embodiments, potassium chloride is present at a concentration of about 100 mM to about 800 mM. In some embodiments, potassium chloride is present at a concentration of about 125 mM to about 800 mM. In some embodiments, potassium chloride is present at a concentration of about 150 mM to about 800 mM. In some embodiments, potassium chloride is present at a concentration of about 175 mM to about 800 mM. In some embodiments, potassium chloride is present at a concentration of about 200 mM to about 800 mM. In some embodiments, potassium chloride is present at a concentration of about 250 mM to about 800 mM. In some embodiments, potassium chloride is present at a concentration of about 300 mM to about 800 mM. In some embodiments, potassium chloride is present at a concentration of about 350 mM to about 800 mM. In some embodiments, potassium chloride is present at a concentration of about 400 mM to about 800 mM. In some embodiments, potassium chloride is present at a concentration of about 500 mM to about 800 mM. In some embodiments, potassium chloride is present at a concentration of about 600 mM to about 800 mM. In some embodiments, potassium chloride is present at a concentration of about 700 mM to about 800 mM.

[0115] In some embodiments, potassium chloride is present at a concentration of about 100 mM. In some embodiments, potassium chloride is present at a concentration of about 110 mM. In some embodiments, potassium chloride is present at a concentration of about 120 mM. In some embodiments, potassium chloride is present at a concentration of about 130 mM. In some embodiments, potassium chloride is present at a concentration of about 140 mM. In some embodiments, potassium chloride is present at a concentration of about 150 mM. In some embodiments, potassium chloride is present at a concentration of about 160 mM. In some embodiments, potassium chloride is present at a concentration of about 170 mM. In some embodiments, potassium chloride is present at a concentration of about 180 mM. In some embodiments, potassium chloride is present at a concentration of about 190 mM. In some embodiments, potassium chloride is present at a concentration of about 200 mM. In some embodiments, potassium chloride is present at a concentration of about 210 mM. In some embodiments, potassium chloride is present at a concentration of about 220 mM. In some embodiments, potassium chloride is present at a concentration of about 230 mM. In some embodiments, potassium chloride is present at a concentration of about 240 mM. In some embodiments, potassium chloride is present at a concentration of about 250 mM. In some embodiments, potassium chloride is present at a concentration of about 260 mM. In some embodiments, potassium chloride is present at a concentration of about 270 mM. In some embodiments, potassium chloride is present at a concentration of about 280 mM. In some embodiments, potassium chloride is present at a concentration of about 290 mM. In some embodiments, potassium chloride is present at a concentration of about 300 mM. In some embodiments, potassium chloride is present at a concentration of about 310 mM. In some embodiments, potassium chloride is present at a concentration of about 320 mM. In some embodiments, potassium chloride is present at a concentration of about 330 mM. In some embodiments, potassium chloride is present at a concentration of about 340 mM. In some embodiments, potassium chloride is present at a concentration of about 350 mM. In some embodiments, potassium chloride is present at a concentration of approximately 360 mM. In some embodiments, potassium chloride is present at a concentration of approximately 370 mM.In some embodiments, potassium chloride is present at a concentration of about 380 mM. In some embodiments, potassium chloride is present at a concentration of about 390 mM. In some embodiments, potassium chloride is present at a concentration of about 400 mM. In some embodiments, potassium chloride is present at a concentration of about 410 mM. In some embodiments, potassium chloride is present at a concentration of about 420 mM. In some embodiments, potassium chloride is present at a concentration of about 430 mM. In some embodiments, potassium chloride is present at a concentration of about 440 mM. In some embodiments, potassium chloride is present at a concentration of about 450 mM. In some embodiments, potassium chloride is present at a concentration of about 460 mM. In some embodiments, potassium chloride is present at a concentration of about 470 mM. In some embodiments, potassium chloride is present at a concentration of about 480 mM. In some embodiments, potassium chloride is present at a concentration of about 490 mM. In some embodiments, potassium chloride is present at a concentration of about 500 mM. In some embodiments, potassium chloride is present at a concentration of about 510 mM. In some embodiments, potassium chloride is present at a concentration of about 520 mM. In some embodiments, potassium chloride is present at a concentration of about 530 mM. In some embodiments, potassium chloride is present at a concentration of about 540 mM. In some embodiments, potassium chloride is present at a concentration of about 550 mM. In some embodiments, potassium chloride is present at a concentration of about 560 mM. In some embodiments, potassium chloride is present at a concentration of about 570 mM. In some embodiments, potassium chloride is present at a concentration of about 580 mM. In some embodiments, potassium chloride is present at a concentration of about 590 mM. In some embodiments, potassium chloride is present at a concentration of about 600 mM. In some embodiments, potassium chloride is present at a concentration of about 610 mM. In some embodiments, potassium chloride is present at a concentration of about 620 mM. In some embodiments, potassium chloride is present at a concentration of about 630 mM. In some embodiments, potassium chloride is present at a concentration of approximately 640 mM. In some embodiments, potassium chloride is present at a concentration of approximately 650 mM.In some embodiments, potassium chloride is present at a concentration of about 660 mM. In some embodiments, potassium chloride is present at a concentration of about 670 mM. In some embodiments, potassium chloride is present at a concentration of about 680 mM. In some embodiments, potassium chloride is present at a concentration of about 690 mM. In some embodiments, potassium chloride is present at a concentration of about 700 mM. In some embodiments, potassium chloride is present at a concentration of about 710 mM. In some embodiments, potassium chloride is present at a concentration of about 720 mM. In some embodiments, potassium chloride is present at a concentration of about 730 mM. In some embodiments, potassium chloride is present at a concentration of about 740 mM. In some embodiments, potassium chloride is present at a concentration of about 750 mM. In some embodiments, potassium chloride is present at a concentration of about 760 mM. In some embodiments, potassium chloride is present at a concentration of about 770 mM. In some embodiments, potassium chloride is present at a concentration of about 780 mM. In some embodiments, potassium chloride is present at a concentration of approximately 790 mM. In some embodiments, potassium chloride is present at a concentration of approximately 800 mM.

[0116] In some embodiments, the pharmaceutically acceptable salt is magnesium chloride.

[0117] In some embodiments, magnesium chloride is present at a concentration of about 100 mM to about 800 mM, or any value or range in between. In some embodiments, magnesium chloride is present at a concentration of about 100 mM to about 700 mM. In some embodiments, magnesium chloride is present at a concentration of about 100 mM to about 600 mM. In some embodiments, magnesium chloride is present at a concentration of about 100 mM to about 500 mM. In some embodiments, magnesium chloride is present at a concentration of about 100 mM to about 400 mM. In some embodiments, magnesium chloride is present at a concentration of about 100 mM to about 300 mM. In some embodiments, magnesium chloride is present at a concentration of about 100 mM to about 250 mM. In some embodiments, magnesium chloride is present at a concentration of about 100 mM to about 200 mM. In some embodiments, magnesium chloride is present at a concentration of about 100 mM to about 175 mM. In some embodiments, magnesium chloride is present at a concentration of about 100 mM to about 150 mM. In some embodiments, magnesium chloride is present at a concentration of about 100 mM to about 125 mM.

[0118] In some embodiments, magnesium chloride is present at a concentration of about 100 mM to about 800 mM. In some embodiments, magnesium chloride is present at a concentration of about 125 mM to about 800 mM. In some embodiments, magnesium chloride is present at a concentration of about 150 mM to about 800 mM. In some embodiments, magnesium chloride is present at a concentration of about 175 mM to about 800 mM. In some embodiments, magnesium chloride is present at a concentration of about 200 mM to about 800 mM. In some embodiments, magnesium chloride is present at a concentration of about 250 mM to about 800 mM. In some embodiments, magnesium chloride is present at a concentration of about 300 mM to about 800 mM. In some embodiments, magnesium chloride is present at a concentration of about 350 mM to about 800 mM. In some embodiments, magnesium chloride is present at a concentration of about 400 mM to about 800 mM. In some embodiments, magnesium chloride is present at a concentration of about 500 mM to about 800 mM. In some embodiments, magnesium chloride is present at a concentration of about 600 mM to about 800 mM. In some embodiments, magnesium chloride is present at a concentration of about 700 mM to about 800 mM.

[0119] In some embodiments, magnesium chloride is present at a concentration of about 100 mM. In some embodiments, magnesium chloride is present at a concentration of about 110 mM. In some embodiments, magnesium chloride is present at a concentration of about 120 mM. In some embodiments, magnesium chloride is present at a concentration of about 130 mM. In some embodiments, magnesium chloride is present at a concentration of about 140 mM. In some embodiments, magnesium chloride is present at a concentration of about 150 mM. In some embodiments, magnesium chloride is present at a concentration of about 160 mM. In some embodiments, magnesium chloride is present at a concentration of about 170 mM. In some embodiments, magnesium chloride is present at a concentration of about 180 mM. In some embodiments, magnesium chloride is present at a concentration of about 190 mM. In some embodiments, magnesium chloride is present at a concentration of about 200 mM. In some embodiments, magnesium chloride is present at a concentration of about 210 mM. In some embodiments, magnesium chloride is present at a concentration of about 220 mM. In some embodiments, magnesium chloride is present at a concentration of about 230 mM. In some embodiments, magnesium chloride is present at a concentration of about 240 mM. In some embodiments, magnesium chloride is present at a concentration of about 250 mM. In some embodiments, magnesium chloride is present at a concentration of about 260 mM. In some embodiments, magnesium chloride is present at a concentration of about 270 mM. In some embodiments, magnesium chloride is present at a concentration of about 280 mM. In some embodiments, magnesium chloride is present at a concentration of about 290 mM. In some embodiments, magnesium chloride is present at a concentration of about 300 mM. In some embodiments, magnesium chloride is present at a concentration of about 310 mM. In some embodiments, magnesium chloride is present at a concentration of about 320 mM. In some embodiments, magnesium chloride is present at a concentration of about 330 mM. In some embodiments, magnesium chloride is present at a concentration of about 340 mM. In some embodiments, magnesium chloride is present at a concentration of about 350 mM. In some embodiments, magnesium chloride is present at a concentration of approximately 360 mM.In some embodiments, magnesium chloride is present at a concentration of about 370 mM. In some embodiments, magnesium chloride is present at a concentration of about 380 mM. In some embodiments, magnesium chloride is present at a concentration of about 390 mM. In some embodiments, magnesium chloride is present at a concentration of about 400 mM. In some embodiments, magnesium chloride is present at a concentration of about 410 mM. In some embodiments, magnesium chloride is present at a concentration of about 420 mM. In some embodiments, magnesium chloride is present at a concentration of about 430 mM. In some embodiments, magnesium chloride is present at a concentration of about 440 mM. In some embodiments, magnesium chloride is present at a concentration of about 450 mM. In some embodiments, magnesium chloride is present at a concentration of about 460 mM. In some embodiments, magnesium chloride is present at a concentration of about 470 mM. In some embodiments, magnesium chloride is present at a concentration of about 480 mM. In some embodiments, magnesium chloride is present at a concentration of about 490 mM. In some embodiments, magnesium chloride is present at a concentration of about 500 mM. In some embodiments, magnesium chloride is present at a concentration of about 510 mM. In some embodiments, magnesium chloride is present at a concentration of about 520 mM. In some embodiments, magnesium chloride is present at a concentration of about 530 mM. In some embodiments, magnesium chloride is present at a concentration of about 540 mM. In some embodiments, magnesium chloride is present at a concentration of about 550 mM. In some embodiments, magnesium chloride is present at a concentration of about 560 mM. In some embodiments, magnesium chloride is present at a concentration of about 570 mM. In some embodiments, magnesium chloride is present at a concentration of about 580 mM. In some embodiments, magnesium chloride is present at a concentration of about 590 mM. In some embodiments, magnesium chloride is present at a concentration of about 600 mM. In some embodiments, magnesium chloride is present at a concentration of about 610 mM. In some embodiments, magnesium chloride is present at a concentration of about 620 mM. In some embodiments, magnesium chloride is present at a concentration of approximately 630 mM.In some embodiments, magnesium chloride is present at a concentration of about 640 mM. In some embodiments, magnesium chloride is present at a concentration of about 650 mM. In some embodiments, magnesium chloride is present at a concentration of about 660 mM. In some embodiments, magnesium chloride is present at a concentration of about 670 mM. In some embodiments, magnesium chloride is present at a concentration of about 680 mM. In some embodiments, magnesium chloride is present at a concentration of about 690 mM. In some embodiments, magnesium chloride is present at a concentration of about 700 mM. In some embodiments, magnesium chloride is present at a concentration of about 710 mM. In some embodiments, magnesium chloride is present at a concentration of about 720 mM. In some embodiments, magnesium chloride is present at a concentration of about 730 mM. In some embodiments, magnesium chloride is present at a concentration of about 740 mM. In some embodiments, magnesium chloride is present at a concentration of about 750 mM. In some embodiments, magnesium chloride is present at a concentration of about 760 mM. In some embodiments, magnesium chloride is present at a concentration of about 770 mM. In some embodiments, magnesium chloride is present at a concentration of about 780 mM. In some embodiments, magnesium chloride is present at a concentration of about 790 mM. In some embodiments, magnesium chloride is present at a concentration of about 800 mM.

[0120] In some embodiments, the pharmaceutically acceptable salt is calcium chloride.

[0121] In some embodiments, calcium chloride is present at a concentration of about 100 mM to about 800 mM, or any value or range in between. In some embodiments, calcium chloride is present at a concentration of about 100 mM to about 700 mM. In some embodiments, calcium chloride is present at a concentration of about 100 mM to about 600 mM. In some embodiments, calcium chloride is present at a concentration of about 100 mM to about 500 mM. In some embodiments, calcium chloride is present at a concentration of about 100 mM to about 400 mM. In some embodiments, calcium chloride is present at a concentration of about 100 mM to about 300 mM. In some embodiments, calcium chloride is present at a concentration of about 100 mM to about 250 mM. In some embodiments, calcium chloride is present at a concentration of about 100 mM to about 200 mM. In some embodiments, calcium chloride is present at a concentration of about 100 mM to about 175 mM. In some embodiments, calcium chloride is present at a concentration of about 100 mM to about 150 mM. In some embodiments, calcium chloride is present at a concentration of about 100 mM to about 125 mM.

[0122] In some embodiments, calcium chloride is present at a concentration of about 100 mM to about 800 mM. In some embodiments, calcium chloride is present at a concentration of about 125 mM to about 800 mM. In some embodiments, calcium chloride is present at a concentration of about 150 mM to about 800 mM. In some embodiments, calcium chloride is present at a concentration of about 175 mM to about 800 mM. In some embodiments, calcium chloride is present at a concentration of about 200 mM to about 800 mM. In some embodiments, calcium chloride is present at a concentration of about 250 mM to about 800 mM. In some embodiments, calcium chloride is present at a concentration of about 300 mM to about 800 mM. In some embodiments, calcium chloride is present at a concentration of about 350 mM to about 800 mM. In some embodiments, calcium chloride is present at a concentration of about 400 mM to about 800 mM. In some embodiments, calcium chloride is present at a concentration of about 500 mM to about 800 mM. In some embodiments, calcium chloride is present at a concentration of about 600 mM to about 800 mM. In some embodiments, calcium chloride is present at a concentration of about 700 mM to about 800 mM.

[0123] In some embodiments, calcium chloride is present at a concentration of about 100 mM. In some embodiments, calcium chloride is present at a concentration of about 110 mM. In some embodiments, calcium chloride is present at a concentration of about 120 mM. In some embodiments, calcium chloride is present at a concentration of about 130 mM. In some embodiments, calcium chloride is present at a concentration of about 140 mM. In some embodiments, calcium chloride is present at a concentration of about 150 mM. In some embodiments, calcium chloride is present at a concentration of about 160 mM. In some embodiments, calcium chloride is present at a concentration of about 170 mM. In some embodiments, calcium chloride is present at a concentration of about 180 mM. In some embodiments, calcium chloride is present at a concentration of about 190 mM. In some embodiments, calcium chloride is present at a concentration of about 200 mM. In some embodiments, calcium chloride is present at a concentration of about 210 mM. In some embodiments, calcium chloride is present at a concentration of about 220 mM. In some embodiments, calcium chloride is present at a concentration of about 230 mM. In some embodiments, calcium chloride is present at a concentration of about 240 mM. In some embodiments, calcium chloride is present at a concentration of about 250 mM. In some embodiments, calcium chloride is present at a concentration of about 260 mM. In some embodiments, calcium chloride is present at a concentration of about 270 mM. In some embodiments, calcium chloride is present at a concentration of about 280 mM. In some embodiments, calcium chloride is present at a concentration of about 290 mM. In some embodiments, calcium chloride is present at a concentration of about 300 mM. In some embodiments, calcium chloride is present at a concentration of about 310 mM. In some embodiments, calcium chloride is present at a concentration of about 320 mM. In some embodiments, calcium chloride is present at a concentration of about 330 mM. In some embodiments, calcium chloride is present at a concentration of about 340 mM. In some embodiments, calcium chloride is present at a concentration of about 350 mM. In some embodiments, calcium chloride is present at a concentration of approximately 360 mM.In some embodiments, calcium chloride is present at a concentration of about 370 mM. In some embodiments, calcium chloride is present at a concentration of about 380 mM. In some embodiments, calcium chloride is present at a concentration of about 390 mM. In some embodiments, calcium chloride is present at a concentration of about 400 mM. In some embodiments, calcium chloride is present at a concentration of about 410 mM. In some embodiments, calcium chloride is present at a concentration of about 420 mM. In some embodiments, calcium chloride is present at a concentration of about 430 mM. In some embodiments, calcium chloride is present at a concentration of about 440 mM. In some embodiments, calcium chloride is present at a concentration of about 450 mM. In some embodiments, calcium chloride is present at a concentration of about 460 mM. In some embodiments, calcium chloride is present at a concentration of about 470 mM. In some embodiments, calcium chloride is present at a concentration of about 480 mM. In some embodiments, calcium chloride is present at a concentration of about 490 mM. In some embodiments, calcium chloride is present at a concentration of about 500 mM. In some embodiments, calcium chloride is present at a concentration of about 510 mM. In some embodiments, calcium chloride is present at a concentration of about 520 mM. In some embodiments, calcium chloride is present at a concentration of about 530 mM. In some embodiments, calcium chloride is present at a concentration of about 540 mM. In some embodiments, calcium chloride is present at a concentration of about 550 mM. In some embodiments, calcium chloride is present at a concentration of about 560 mM. In some embodiments, calcium chloride is present at a concentration of about 570 mM. In some embodiments, calcium chloride is present at a concentration of about 580 mM. In some embodiments, calcium chloride is present at a concentration of about 590 mM. In some embodiments, calcium chloride is present at a concentration of about 600 mM. In some embodiments, calcium chloride is present at a concentration of about 610 mM. In some embodiments, calcium chloride is present at a concentration of about 620 mM. In some embodiments, calcium chloride is present at a concentration of approximately 630 mM.In some embodiments, calcium chloride is present at a concentration of about 640 mM. In some embodiments, calcium chloride is present at a concentration of about 650 mM. In some embodiments, calcium chloride is present at a concentration of about 660 mM. In some embodiments, calcium chloride is present at a concentration of about 670 mM. In some embodiments, calcium chloride is present at a concentration of about 680 mM. In some embodiments, calcium chloride is present at a concentration of about 690 mM. In some embodiments, calcium chloride is present at a concentration of about 700 mM. In some embodiments, calcium chloride is present at a concentration of about 710 mM. In some embodiments, calcium chloride is present at a concentration of about 720 mM. In some embodiments, calcium chloride is present at a concentration of about 730 mM. In some embodiments, calcium chloride is present at a concentration of about 740 mM. In some embodiments, calcium chloride is present at a concentration of about 750 mM. In some embodiments, calcium chloride is present at a concentration of about 760 mM. In some embodiments, calcium chloride is present at a concentration of about 770 mM. In some embodiments, calcium chloride is present at a concentration of about 780 mM. In some embodiments, calcium chloride is present at a concentration of about 790 mM. In some embodiments, calcium chloride is present at a concentration of about 800 mM.

[0124] In some embodiments, the sugar is present at about 1% (w / v) to about 10% (w / v), or any value or range therebetween.

[0125] In some embodiments, the sugar is present at about 1% (w / v) to about 10% (w / v). In some embodiments, the sugar is present at about 1% (w / v) to about 8% (w / v). In some embodiments, the sugar is present at about 1% (w / v) to about 7% (w / v). In some embodiments, the sugar is present at about 1% (w / v) to about 6% (w / v). In some embodiments, the sugar is present at about 1% (w / v) to about 5% (w / v). In some embodiments, the sugar is present at about 1% (w / v) to about 4% (w / v). In some embodiments, the sugar is present at about 2% (w / v) to about 4% (w / v). In some embodiments, the sugar is present at about 1% (w / v) to about 3% (w / v). In some embodiments, the sugar is present at about 1% (w / v) to about 2% (w / v).

[0126] In some embodiments, the sugar is present at about 1% (w / v) to about 10% (w / v). In some embodiments, the sugar is present at about 2% (w / v) to about 10% (w / v). In some embodiments, the sugar is present at about 3% (w / v) to about 10% (w / v). In some embodiments, the sugar is present at about 4% (w / v) to about 10% (w / v). In some embodiments, the sugar is present at about 5% (w / v) to about 10% (w / v). In some embodiments, the sugar is present at about 6% (w / v) to about 10% (w / v). In some embodiments, the sugar is present at about 7% (w / v) to about 10% (w / v). In some embodiments, the sugar is present at about 8% (w / v) to about 10% (w / v). In some embodiments, the sugar is present at about 9% (w / v) to about 10% (w / v).

[0127] In some embodiments, sugar is present at approximately 1% (w / v). In some embodiments, sugar is present at approximately 2% (w / v). In some embodiments, sugar is present at approximately 3% (w / v). In some embodiments, sugar is present at approximately 4% (w / v). In some embodiments, sugar is present at approximately 5% (w / v). In some embodiments, sugar is present at approximately 6% (w / v). In some embodiments, sugar is present at approximately 7% (w / v). In some embodiments, sugar is present at approximately 8% (w / v). In some embodiments, sugar is present at approximately 9% (w / v). In some embodiments, sugar is present at approximately 10% (w / v).

[0128] In some embodiments, the sugar is selected from sucrose, trehalose, mannose, glucose, sorbitol, mannitol, or a combination thereof.

[0129] In some embodiments, the sugar is sucrose. In some embodiments, the sugar is trehalose. In some embodiments, the sugar is mannose. In some embodiments, the sugar is glucose. In some embodiments, the sugar is sorbitol. In some embodiments, the sugar is mannitol.

[0130] In some embodiments, the sugar is sucrose.

[0131] In some embodiments, sucrose is present in an amount of approximately 1%(w / v) to approximately 10%(w / v), or any value or range in between. In some embodiments, sucrose is present in an amount of approximately 1%(w / v) to approximately 9%(w / v). In some embodiments, sucrose is present in an amount of approximately 1%(w / v) to approximately 8%(w / v). In some embodiments, sucrose is present in an amount of approximately 1%(w / v) to approximately 7%(w / v). In some embodiments, sucrose is present in an amount of approximately 1%(w / v) to approximately 6%(w / v). In some embodiments, sucrose is present in an amount of approximately 1%(w / v) to approximately 5%(w / v). In some embodiments, sucrose is present in an amount of approximately 1%(w / v) to approximately 4%(w / v). In some embodiments, sucrose is present in an amount of approximately 2%(w / v) to approximately 4%(w / v). In some embodiments, sucrose is present at a concentration of approximately 1% (w / v) to approximately 3% (w / v). In some embodiments, sucrose is present at a concentration of approximately 1% (w / v) to approximately 2% (w / v).

[0132] In some embodiments, sucrose is present at approximately 1% (w / v) to approximately 10% (w / v). In some embodiments, sucrose is present at approximately 2% (w / v) to approximately 10% (w / v). In some embodiments, sucrose is present at approximately 3% (w / v) to approximately 10% (w / v). In some embodiments, sucrose is present at approximately 4% (w / v) to approximately 10% (w / v). In some embodiments, sucrose is present at approximately 5% (w / v) to approximately 10% (w / v). In some embodiments, sucrose is present at approximately 6% (w / v) to approximately 10% (w / v). In some embodiments, sucrose is present at approximately 7% (w / v) to approximately 10% (w / v). In some embodiments, sucrose is present at approximately 8% (w / v) to approximately 10% (w / v). In some embodiments, sucrose is present at approximately 9% (w / v) to 10% (w / v).

[0133] In some embodiments, sucrose is present at approximately 1% (w / v). In some embodiments, sucrose is present at approximately 2% (w / v). In some embodiments, sucrose is present at approximately 3% (w / v). In some embodiments, sucrose is present at approximately 4% (w / v). In some embodiments, sucrose is present at approximately 5% (w / v). In some embodiments, sucrose is present at approximately 6% (w / v). In some embodiments, sucrose is present at approximately 7% (w / v). In some embodiments, sucrose is present at approximately 8% (w / v). In some embodiments, sucrose is present at approximately 9% (w / v). In some embodiments, sucrose is present at approximately 10% (w / v).

[0134] In some embodiments, sucrose is present at approximately 4% (w / v).

[0135] In some embodiments, the sugar is trehalose.

[0136] In some embodiments, trehalose is present in an amount of approximately 1% (w / v) to approximately 10% (w / v), or any value or range in between. In some embodiments, trehalose is present in an amount of approximately 1% (w / v) to approximately 9% (w / v). In some embodiments, trehalose is present in an amount of approximately 1% (w / v) to approximately 8% (w / v). In some embodiments, trehalose is present in an amount of approximately 1% (w / v) to approximately 7% (w / v). In some embodiments, trehalose is present in an amount of approximately 1% (w / v) to approximately 6% (w / v). In some embodiments, trehalose is present in an amount of approximately 1% (w / v) to approximately 5% (w / v). In some embodiments, trehalose is present in an amount of approximately 1% (w / v) to approximately 4% (w / v). In some embodiments, trehalose is present in an amount of approximately 2% (w / v) to approximately 4% (w / v). In some embodiments, trehalose is present at a concentration of approximately 1% (w / v) to approximately 3% (w / v). In some embodiments, trehalose is present at a concentration of approximately 1% (w / v) to approximately 2% (w / v).

[0137] In some embodiments, trehalose is present at approximately 1% (w / v) to approximately 10% (w / v). In some embodiments, trehalose is present at approximately 2% (w / v) to approximately 10% (w / v). In some embodiments, trehalose is present at approximately 3% (w / v) to approximately 10% (w / v). In some embodiments, trehalose is present at approximately 4% (w / v) to approximately 10% (w / v). In some embodiments, trehalose is present at approximately 5% (w / v) to approximately 10% (w / v). In some embodiments, trehalose is present at approximately 6% (w / v) to approximately 10% (w / v). In some embodiments, trehalose is present at approximately 7% (w / v) to approximately 10% (w / v). In some embodiments, trehalose is present at approximately 8% (w / v) to approximately 10% (w / v). In some embodiments, trehalose is present at approximately 9% (w / v) to approximately 10% (w / v).

[0138] In some embodiments, trehalose is present at approximately 1% (w / v). In some embodiments, trehalose is present at approximately 2% (w / v). In some embodiments, trehalose is present at approximately 3% (w / v). In some embodiments, trehalose is present at approximately 4% (w / v). In some embodiments, trehalose is present at approximately 5% (w / v). In some embodiments, trehalose is present at approximately 6% (w / v). In some embodiments, trehalose is present at approximately 7% (w / v). In some embodiments, trehalose is present at approximately 8% (w / v). In some embodiments, trehalose is present at approximately 9% (w / v). In some embodiments, trehalose is present at approximately 10% (w / v).

[0139] In some embodiments, the sugar is mannose.

[0140] In some embodiments, mannose is present in an amount of approximately 1%(w / v) to approximately 10%(w / v), or any value or range in between. In some embodiments, mannose is present in an amount of approximately 1%(w / v) to approximately 9%(w / v). In some embodiments, mannose is present in an amount of approximately 1%(w / v) to approximately 8%(w / v). In some embodiments, mannose is present in an amount of approximately 1%(w / v) to approximately 7%(w / v). In some embodiments, mannose is present in an amount of approximately 1%(w / v) to approximately 6%(w / v). In some embodiments, mannose is present in an amount of approximately 1%(w / v) to approximately 5%(w / v). In some embodiments, mannose is present in an amount of approximately 1%(w / v) to approximately 4%(w / v). In some embodiments, mannose is present in an amount of approximately 2%(w / v) to approximately 4%(w / v). In some embodiments, mannose is present at a concentration of approximately 1% (w / v) to approximately 3% (w / v). In some embodiments, mannose is present at a concentration of approximately 1% (w / v) to approximately 2% (w / v).

[0141] In some embodiments, mannose is present at approximately 1% (w / v) to approximately 10% (w / v). In some embodiments, mannose is present at approximately 2% (w / v) to approximately 10% (w / v). In some embodiments, mannose is present at approximately 3% (w / v) to approximately 10% (w / v). In some embodiments, mannose is present at approximately 4% (w / v) to approximately 10% (w / v). In some embodiments, mannose is present at approximately 5% (w / v) to approximately 10% (w / v). In some embodiments, mannose is present at approximately 6% (w / v) to approximately 10% (w / v). In some embodiments, mannose is present at approximately 7% (w / v) to approximately 10% (w / v). In some embodiments, mannose is present at approximately 8% (w / v) to approximately 10% (w / v). In some embodiments, mannose is present at approximately 9% (w / v) to 10% (w / v).

[0142] In some embodiments, mannose is present at approximately 1% (w / v). In some embodiments, mannose is present at approximately 2% (w / v). In some embodiments, mannose is present at approximately 3% (w / v). In some embodiments, mannose is present at approximately 4% (w / v). In some embodiments, mannose is present at approximately 5% (w / v). In some embodiments, mannose is present at approximately 6% (w / v). In some embodiments, mannose is present at approximately 7% (w / v). In some embodiments, mannose is present at approximately 8% (w / v). In some embodiments, mannose is present at approximately 9% (w / v). In some embodiments, mannose is present at approximately 10% (w / v).

[0143] In some embodiments, the sugar is glucose.

[0144] In some embodiments, glucose is present in an amount of approximately 1% (w / v) to approximately 10% (w / v), or any value or range in between. In some embodiments, glucose is present in an amount of approximately 1% (w / v) to approximately 9% (w / v). In some embodiments, glucose is present in an amount of approximately 1% (w / v) to approximately 8% (w / v). In some embodiments, glucose is present in an amount of approximately 1% (w / v) to approximately 7% (w / v). In some embodiments, glucose is present in an amount of approximately 1% (w / v) to approximately 6% (w / v). In some embodiments, glucose is present in an amount of approximately 1% (w / v) to approximately 5% (w / v). In some embodiments, glucose is present in an amount of approximately 1% (w / v) to approximately 4% (w / v). In some embodiments, glucose is present in an amount of approximately 2% (w / v) to approximately 4% (w / v). In some embodiments, glucose is present in an amount of approximately 1% (w / v) to approximately 3% (w / v). In some embodiments, glucose is present at approximately 1% (w / v) to approximately 2% (w / v).

[0145] In some embodiments, glucose is present at about 1% (w / v) to about 10% (w / v). In some embodiments, glucose is present at about 2% (w / v) to about 10% (w / v). In some embodiments, glucose is present at about 3% (w / v) to about 10% (w / v). In some embodiments, glucose is present at about 4% (w / v) to about 10% (w / v). In some embodiments, glucose is present at about 5% (w / v) to about 10% (w / v). In some embodiments, glucose is present at about 6% (w / v) to about 10% (w / v). In some embodiments, glucose is present at about 7% (w / v) to about 10% (w / v). In some embodiments, glucose is present at about 8% (w / v) to about 10% (w / v). In some embodiments, glucose is present at about 9% (w / v) to about 10% (w / v).

[0146] In some embodiments, glucose is present at about 1% (w / v). In some embodiments, glucose is present at about 2% (w / v). In some embodiments, glucose is present at about 3% (w / v). In some embodiments, glucose is present at about 4% (w / v). In some embodiments, glucose is present at about 5% (w / v). In some embodiments, glucose is present at about 6% (w / v). In some embodiments, glucose is present at about 7% (w / v). In some embodiments, glucose is present at about 8% (w / v). In some embodiments, glucose is present at about 9% (w / v). In some embodiments, glucose is present at about 10% (w / v).

[0147] In some embodiments, the sugar is sorbitol.

[0148] In some embodiments, sorbitol is present in an amount of approximately 1% (w / v) to approximately 10% (w / v), or any value or range in between. In some embodiments, sorbitol is present in an amount of approximately 1% (w / v) to approximately 9% (w / v). In some embodiments, sorbitol is present in an amount of approximately 1% (w / v) to approximately 8% (w / v). In some embodiments, sorbitol is present in an amount of approximately 1% (w / v) to approximately 7% (w / v). In some embodiments, sorbitol is present in an amount of approximately 1% (w / v) to approximately 6% (w / v). In some embodiments, sorbitol is present in an amount of approximately 1% (w / v) to approximately 5% (w / v). In some embodiments, sorbitol is present in an amount of approximately 1% (w / v) to approximately 4% (w / v). In some embodiments, sorbitol is present in an amount of approximately 2% (w / v) to approximately 4% (w / v). In some embodiments, sorbitol is present at a concentration of approximately 1% (w / v) to approximately 3% (w / v). In some embodiments, sorbitol is present at a concentration of approximately 1% (w / v) to approximately 2% (w / v).

[0149] In some embodiments, sorbitol is present in an amount of approximately 1% (w / v) to approximately 10% (w / v). In some embodiments, sorbitol is present in an amount of approximately 2% (w / v) to approximately 10% (w / v). In some embodiments, sorbitol is present in an amount of approximately 3% (w / v) to approximately 10% (w / v). In some embodiments, sorbitol is present in an amount of approximately 4% (w / v) to approximately 10% (w / v). In some embodiments, sorbitol is present in an amount of approximately 5% (w / v) to approximately 10% (w / v). In some embodiments, sorbitol is present in an amount of approximately 6% (w / v) to approximately 10% (w / v). In some embodiments, sorbitol is present in an amount of approximately 7% (w / v) to approximately 10% (w / v). In some embodiments, sorbitol is present in an amount of approximately 8% (w / v) to approximately 10% (w / v). In some embodiments, sorbitol is present at approximately 9% (w / v) to approximately 10% (w / v).

[0150] In some embodiments, sorbitol is present at approximately 1% (w / v). In some embodiments, sorbitol is present at approximately 2% (w / v). In some embodiments, sorbitol is present at approximately 3% (w / v). In some embodiments, sorbitol is present at approximately 4% (w / v). In some embodiments, sorbitol is present at approximately 5% (w / v). In some embodiments, sorbitol is present at approximately 6% (w / v). In some embodiments, sorbitol is present at approximately 7% (w / v). In some embodiments, sorbitol is present at approximately 8% (w / v). In some embodiments, sorbitol is present at approximately 9% (w / v). In some embodiments, sorbitol is present at approximately 10% (w / v).

[0151] In some embodiments, the sugar is mannitol.

[0152] In some embodiments, mannitol is present in an amount of approximately 1% (w / v) to approximately 10% (w / v), or any value or range in between. In some embodiments, mannitol is present in an amount of approximately 1% (w / v) to approximately 9% (w / v). In some embodiments, mannitol is present in an amount of approximately 1% (w / v) to approximately 8% (w / v). In some embodiments, mannitol is present in an amount of approximately 1% (w / v) to approximately 7% (w / v). In some embodiments, mannitol is present in an amount of approximately 1% (w / v) to approximately 6% (w / v). In some embodiments, mannitol is present in an amount of approximately 1% (w / v) to approximately 5% (w / v). In some embodiments, mannitol is present in an amount of approximately 1% (w / v) to approximately 4% (w / v). In some embodiments, mannitol is present in an amount of approximately 2% (w / v) to approximately 4% (w / v). In some embodiments, mannitol is present at a concentration of approximately 1% (w / v) to approximately 3% (w / v). In some embodiments, mannitol is present at a concentration of approximately 1% (w / v) to approximately 2% (w / v).

[0153] In some embodiments, mannitol is present at approximately 1% (w / v) to approximately 10% (w / v). In some embodiments, mannitol is present at approximately 2% (w / v) to approximately 10% (w / v). In some embodiments, mannitol is present at approximately 3% (w / v) to approximately 10% (w / v). In some embodiments, mannitol is present at approximately 4% (w / v) to approximately 10% (w / v). In some embodiments, mannitol is present at approximately 5% (w / v) to approximately 10% (w / v). In some embodiments, mannitol is present at approximately 6% (w / v) to approximately 10% (w / v). In some embodiments, mannitol is present at approximately 7% (w / v) to approximately 10% (w / v). In some embodiments, mannitol is present at approximately 8% (w / v) to approximately 10% (w / v). In some embodiments, mannitol is present at approximately 9% (w / v) to 10% (w / v).

[0154] In some embodiments, mannitol is present at approximately 1% (w / v). In some embodiments, mannitol is present at approximately 2% (w / v). In some embodiments, mannitol is present at approximately 3% (w / v). In some embodiments, mannitol is present at approximately 4% (w / v). In some embodiments, mannitol is present at approximately 5% (w / v). In some embodiments, mannitol is present at approximately 6% (w / v). In some embodiments, mannitol is present at approximately 7% (w / v). In some embodiments, mannitol is present at approximately 8% (w / v). In some embodiments, mannitol is present at approximately 9% (w / v). In some embodiments, mannitol is present at approximately 10% (w / v).

[0155] In some embodiments, the pharmaceutically acceptable salt is sodium chloride and the sugar is sucrose.

[0156] In some embodiments, the pharmaceutically acceptable salt is sodium chloride and the sugar is trehalose.

[0157] In some embodiments, the pharmaceutically acceptable salt is sodium chloride and the sugar is mannose.

[0158] In some embodiments, the pharmaceutically acceptable salt is sodium chloride and the sugar is glucose.

[0159] In some embodiments, the pharmaceutically acceptable salt is sodium chloride and the sugar is sorbitol.

[0160] In some embodiments, the pharmaceutically acceptable salt is sodium chloride and the sugar is mannitol.

[0161] In some embodiments, the pharmaceutically acceptable salt is potassium chloride and the sugar is sucrose.

[0162] In some embodiments, the pharmaceutically acceptable salt is potassium chloride and the sugar is trehalose.

[0163] In some embodiments, the pharmaceutically acceptable salt is potassium chloride and the sugar is mannose.

[0164] In some embodiments, the pharmaceutically acceptable salt is potassium chloride and the sugar is glucose.

[0165] In some embodiments, the pharmaceutically acceptable salt is potassium chloride and the sugar is sorbitol.

[0166] In some embodiments, the pharmaceutically acceptable salt is potassium chloride and the sugar is mannitol.

[0167] In some embodiments, the pharmaceutically acceptable salt is magnesium chloride and the sugar is sucrose.

[0168] In some embodiments, the pharmaceutically acceptable salt is magnesium chloride, and the sugar is trehalose.

[0169] In some embodiments, the pharmaceutically acceptable salt is magnesium chloride and the sugar is mannose.

[0170] In some embodiments, the pharmaceutically acceptable salt is magnesium chloride and the sugar is glucose.

[0171] In some embodiments, the pharmaceutically acceptable salt is magnesium chloride and the sugar is sorbitol.

[0172] In some embodiments, the pharmaceutically acceptable salt is magnesium chloride, and the sugar is mannitol.

[0173] In some embodiments, the pharmaceutically acceptable salt is calcium chloride and the sugar is sucrose.

[0174] In some embodiments, the pharmaceutically acceptable salt is calcium chloride and the sugar is trehalose.

[0175] In some embodiments, the pharmaceutically acceptable salt is calcium chloride and the sugar is mannose.

[0176] In some embodiments, the pharmaceutically acceptable salt is calcium chloride and the sugar is glucose.

[0177] In some embodiments, the pharmaceutically acceptable salt is calcium chloride and the sugar is sorbitol.

[0178] In some embodiments, the pharmaceutically acceptable salt is calcium chloride and the sugar is mannitol.

[0179] In some embodiments, the protein excipient is selected from, but is not limited to, myoglobulin, serum albumin, bovine serum albumin, human serum albumin, immunoglobulin, immunoglobulin fragments, fibronectin, vitronectin, or a combination thereof. In some embodiments, the protein excipient comprises serum albumin. In some embodiments, the protein excipient comprises human serum albumin. In some embodiments, the human serum albumin is recombinant human serum albumin. In some embodiments, the human serum albumin is non-recombinant human serum albumin. In some embodiments, the non-recombinant human serum albumin is United States Pharmacopeia (USP) grade non-recombinant human serum albumin. In some embodiments, the non-recombinant human serum albumin is FDA-approved non-recombinant human serum albumin.

[0180] In some embodiments, the protein excipient is recombinant human serum albumin. In some embodiments, the protein excipient is non-recombinant human serum albumin.

[0181] In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 3% (w / v), or any value or range in between. In some embodiments, the protein excipient is present in an amount of about 0.2% (w / v) to about 3% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.3% (w / v) to about 3% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.4% (w / v) to about 3% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.5% (w / v) to about 3% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.6% (w / v) to about 3% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.7% (w / v) to about 3% (w / v). In some embodiments, the protein excipient is present in an amount of approximately 0.8% (w / v) to approximately 3% (w / v). In some embodiments, the protein excipient is present in an amount of approximately 0.9% (w / v) to approximately 3% (w / v). In some embodiments, the protein excipient is present in an amount of approximately 1% (w / v) to approximately 3% (w / v). In some embodiments, the protein excipient is present in an amount of approximately 1.2% (w / v) to approximately 3% (w / v). In some embodiments, the protein excipient is present in an amount of approximately 1.4% (w / v) to approximately 3% (w / v). In some embodiments, the protein excipient is present in an amount of approximately 1.5% (w / v) to approximately 3% (w / v). In some embodiments, the protein excipient is present in an amount of approximately 1.6% (w / v) to approximately 3% (w / v). In some embodiments, the protein excipient is present in an amount of approximately 1.8% (w / v) to approximately 3% (w / v). In some embodiments, the protein excipient is present at approximately 2% (w / v) to approximately 3% (w / v). In some embodiments, the protein excipient is present at approximately 2.2% (w / v) to approximately 3% (w / v). In some embodiments, the protein excipient is present at approximately 2.4% (w / v) to approximately 3% (w / v). In some embodiments, the protein excipient is present at approximately 2.5% (w / v) to approximately 3% (w / v). In some embodiments, the protein excipient is present at approximately 2.6% (w / v) to approximately 3% (w / v). In some embodiments, the protein excipient is present at approximately 2.8% (w / v) to approximately 3% (w / v).

[0182] In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 3% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 2.8% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 2.6% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 2.5% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 2.4% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 2.2% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 2% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 1.8% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 1.6% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 1.5% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 1.4% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 1.2% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 1% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 0.9% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 0.8% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 0.7% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 0.6% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 0.5% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 0.4% (w / v). In some embodiments, the protein excipient is present in an amount of about 0.1% (w / v) to about 0.3% (w / v).In some embodiments, the protein excipient is present at a concentration of approximately 0.1% (w / v) to approximately 0.2% (w / v).

[0183] In some embodiments, the protein excipients are present in amounts of approximately 0.1% (w / v), 0.2% (w / v), 0.3% (w / v), 0.4% (w / v), 0.5% (w / v), 0.6% (w / v), 0.7% (w / v), 0.8% (w / v), 0.9% (w / v), 1% (w / v), 1.1% (w / v), 1.2% (w / v), 1.3% (w / v), 1.4% (w / v), and 1. It is present in 5%(w / v), approximately 1.6%(w / v), approximately 1.7%(w / v), approximately 1.8%(w / v), approximately 1.9%(w / v), approximately 2%(w / v), approximately 2.1%(w / v), approximately 2.2%(w / v), approximately 2.3%(w / v), approximately 2.4%(w / v), approximately 2.5%(w / v), approximately 2.6%(w / v), approximately 2.7%(w / v), approximately 2.8%(w / v), approximately 2.9%(w / v), or approximately 3%(w / v).

[0184] In some embodiments, the protein excipient is present at approximately 0.1% (w / v). In some embodiments, the protein excipient is present at approximately 0.2% (w / v). In some embodiments, the protein excipient is present at approximately 0.3% (w / v). In some embodiments, the protein excipient is present at approximately 0.4% (w / v). In some embodiments, the protein excipient is present at approximately 0.5% (w / v). In some embodiments, the protein excipient is present at approximately 0.6% (w / v). In some embodiments, the protein excipient is present at approximately 0.7% (w / v). In some embodiments, the protein excipient is present at approximately 0.8% (w / v). In some embodiments, the protein excipient is present at approximately 0.9% (w / v). In some embodiments, the protein excipient is present at approximately 1% (w / v). In some embodiments, the protein excipient is present at approximately 1.1% (w / v). In some embodiments, the protein excipient is present at approximately 1.2% (w / v). In some embodiments, the protein excipient is present at approximately 1.3% (w / v). In some embodiments, the protein excipient is present at approximately 1.4% (w / v). In some embodiments, the protein excipient is present at approximately 1.5% (w / v). In some embodiments, the protein excipient is present at approximately 1.6% (w / v). In some embodiments, the protein excipient is present at approximately 1.7% (w / v). In some embodiments, the protein excipient is present at approximately 1.8% (w / v). In some embodiments, the protein excipient is present at approximately 1.9% (w / v). In some embodiments, the protein excipient is present at approximately 2.0% (w / v). In some embodiments, the protein excipient is present at approximately 2.1% (w / v). In some embodiments, the protein excipient is present at approximately 2.2% (w / v). In some embodiments, the protein excipient is present at approximately 2.3% (w / v). In some embodiments, the protein excipient is present at approximately 2.4% (w / v). In some embodiments, the protein excipient is present at approximately 2.5% (w / v). In some embodiments, the protein excipient is present at approximately 2.6% (w / v).In some embodiments, the protein excipient is present at approximately 2.7% (w / v). In some embodiments, the protein excipient is present at approximately 2.8% (w / v). In some embodiments, the protein excipient is present at approximately 2.9% (w / v). In some embodiments, the protein excipient is present at approximately 3.0% (w / v).

[0185] In some embodiments, the protein excipient is present at approximately 0.5%. In some embodiments, the protein excipient is present at approximately 1%.

[0186] In some embodiments, the protein excipient is recombinant human serum albumin. Recombinant human serum albumin can be produced from any source. Methods for preparing recombinant human serum albumin are known in the art, and any such method is within the scope of this application. In some embodiments, human serum albumin is produced recombinantly from a bacterial source (e.g., bacterial cells). In some embodiments, recombinant human serum albumin is produced recombinantly from an insect source (e.g., insect cells). In some embodiments, recombinant human serum albumin is produced recombinantly from a mammalian source (e.g., mammalian cells). In some embodiments, recombinant human serum albumin is produced recombinantly from a plant source. For example, albumin can be produced from plants such as monocots. One non-limiting example of a monocot that may be used is rice. Examples of such production systems can be found in U.S. Patents 10,618,951, 7,304,208, and 8,686,225, which are incorporated herein by reference in their entirety. In some embodiments, the albumin contains a plant glycosyl group which may be referred to as plant glycosylated human serum albumin protein.

[0187] In some embodiments, recombinant human serum albumin is any recombinant human serum albumin. In some embodiments, recombinant human serum albumin is plant glycosylated human serum albumin. In some embodiments, human serum albumin is free from blood (e.g., human blood) or animal contaminants. This can be achieved by producing HSA in monocotyledonous plants or plants such as rice, as provided herein. In some embodiments, recombinant human serum albumin is marketed under the names Exbumin® (recombinant human albumin-Invitria), Cellastim S (recombinant human serum albumin-Invitria), Albagen (recombinant human albumin-Albumin Bioscience), Recombumin (recombinant human albumin-Albumedix), or Optibumin (recombinant human albumin-Invitria). In some embodiments, recombinant human serum albumin is Exbumin®. In some embodiments, recombinant human serum albumin is Cellastim S. In some embodiments, recombinant human serum albumin is Albagen. In some embodiments, recombinant human serum albumin is Recombumin. In some embodiments, recombinant human serum albumin is Optibumin.

[0188] In some embodiments, recombinant human serum albumin is present in a concentration of approximately 0.1% (w / v) to approximately 3% (w / v), or any value or range in between. In some embodiments, recombinant human serum albumin is present in a concentration of approximately 0.2% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present in a concentration of approximately 0.3% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present in a concentration of approximately 0.4% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present in a concentration of approximately 0.5% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present in a concentration of approximately 0.6% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present in a concentration of approximately 0.7% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 0.8% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 0.9% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1.2% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1.4% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1.5% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1.6% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1.8% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2.2% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2.4% (w / v) to approximately 3% (w / v).In some embodiments, recombinant human serum albumin is present at approximately 2.5% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2.6% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2.8% (w / v) to approximately 3% (w / v).

[0189] In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 3% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 2.8% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 2.6% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 2.5% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 2.4% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 2.2% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 2.0% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 1.8% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 1.6% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 1.5% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 1.4% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 1.2% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 1.0% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 0.9% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 0.8% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 0.7% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 0.6% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 0.5% (w / v).In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 0.4% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 0.3% (w / v). In some embodiments, recombinant human serum albumin is present at a concentration of approximately 0.1% (w / v) to approximately 0.2% (w / v).

[0190] In some embodiments, recombinant human serum albumin is present in concentrations of approximately 0.1% (w / v), 0.2% (w / v), 0.3% (w / v), 0.4% (w / v), 0.5% (w / v), 0.6% (w / v), 0.7% (w / v), 0.8% (w / v), 0.9% (w / v), 1% (w / v), 1.1% (w / v), 1.2% (w / v), 1.3% (w / v), 1.4% (w / v), and approximately It is present in approximately 1.5% (w / v), 1.6% (w / v), 1.7% (w / v), 1.8% (w / v), 1.9% (w / v), 2% (w / v), 2.1% (w / v), 2.2% (w / v), 2.3% (w / v), 2.4% (w / v), 2.5% (w / v), 2.6% (w / v), 2.7% (w / v), 2.8% (w / v), 2.9% (w / v), or 3% (w / v).

[0191] In some embodiments, recombinant human serum albumin is present at approximately 0.1% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 0.2% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 0.3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 0.4% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 0.5% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 0.6% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 0.7% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 0.8% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 0.9% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1.1% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1.2% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1.3% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1.4% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1.5% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1.6% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1.7% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1.8% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1.9% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2.1% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2.2% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2.3% (w / v).In some embodiments, recombinant human serum albumin is present at approximately 2.4% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2.5% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2.6% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2.7% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2.8% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 2.9% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 3% (w / v).

[0192] In some embodiments, recombinant human serum albumin is present at approximately 0.5% (w / v). In some embodiments, recombinant human serum albumin is present at approximately 1% (w / v).

[0193] In some embodiments, the protein excipient is recombinant human serum albumin. In some embodiments, the recombinant human serum albumin is any recombinant human serum albumin provided herein. In some embodiments, the recombinant human serum albumin is Exbumin®. In some embodiments, the protein excipient is Exbumin®.

[0194] In some embodiments, Exbumin® is present in a quantity of approximately 0.1%(w / v) to 3%(w / v), or any value or range in between. In some embodiments, Exbumin® is present in a quantity of approximately 0.2%(w / v) to 3%(w / v). In some embodiments, Exbumin® is present in a quantity of approximately 0.3%(w / v) to 3%(w / v). In some embodiments, Exbumin® is present in a quantity of approximately 0.4%(w / v) to 3%(w / v). In some embodiments, Exbumin® is present in a quantity of approximately 0.5%(w / v) to 3%(w / v). In some embodiments, Exbumin® is present in a quantity of approximately 0.6%(w / v) to 3%(w / v). In some embodiments, Exbumin® is present in a quantity of approximately 0.7%(w / v) to 3%(w / v). In some embodiments, Exbumin® is present at approximately 0.8% (w / v) to approximately 3% (w / v). In some embodiments, Exbumin® is present at approximately 0.9% (w / v) to approximately 3% (w / v). In some embodiments, Exbumin® is present at approximately 1% (w / v) to approximately 3% (w / v). In some embodiments, Exbumin® is present at approximately 1.2% (w / v) to approximately 3% (w / v). In some embodiments, Exbumin® is present at approximately 1.4% (w / v) to approximately 3% (w / v). In some embodiments, Exbumin® is present at approximately 1.5% (w / v) to approximately 3% (w / v). In some embodiments, Exbumin® is present at approximately 1.6% (w / v) to approximately 3% (w / v). In some embodiments, Exbumin® is present at approximately 1.8% (w / v) to approximately 3% (w / v). In some embodiments, Exbumin® is present at approximately 2% (w / v) to approximately 3% (w / v). In some embodiments, Exbumin® is present at approximately 2.2% (w / v) to approximately 3% (w / v). In some embodiments, Exbumin® is present at approximately 2.4% (w / v) to approximately 3% (w / v). In some embodiments, Exbumin® is present at approximately 2.5% (w / v) to approximately 3% (w / v).In some embodiments, Exbumin® is present at a concentration of approximately 2.6% (w / v) to approximately 3% (w / v). In some embodiments, Exbumin® is present at a concentration of approximately 2.8% (w / v) to approximately 3% (w / v).

[0195] In some embodiments, Exbumin® is present at a concentration of approximately 0.1% (w / v) to approximately 3% (w / v). In some embodiments, Exbumin® is present at a concentration of approximately 0.1% (w / v) to approximately 2.8% (w / v). In some embodiments, Exbumin® is present at a concentration of approximately 0.1% (w / v) to approximately 2.6% (w / v). In some embodiments, Exbumin® is present at a concentration of approximately 0.1% (w / v) to approximately 2.5% (w / v). In some embodiments, Exbumin® is present at a concentration of approximately 0.1% (w / v) to approximately 2.4% (w / v). In some embodiments, Exbumin® is present at a concentration of approximately 0.1% (w / v) to approximately 2.2% (w / v). In some embodiments, Exbumin® is present at a concentration of approximately 0.1% (w / v) to approximately 2% (w / v). In some embodiments, Exbumin® is present at a concentration of approximately 0.1% (w / v) to approximately 1.8% (w / v). In some embodiments, Exbumin® is present at a concentration of approximately 0.1% (w / v) to approximately 1.6% (w / v). In some embodiments, Exbumin® is present at a concentration of approximately 0.1% (w / v) to approximately 1.5% (w / v). In some embodiments, Exbumin® is present at a concentration of approximately 0.1% (w / v) to approximately 1.4% (w / v). In some embodiments, Exbumin® is present at a concentration of approximately 0.1% (w / v) to approximately 1.2% (w / v). In some embodiments, Exbumin® is present at a concentration of approximately 0.1% (w / v) to approximately 1% (w / v). In some embodiments, Exbumin® is present at a concentration of approximately 0.1% (w / v) to approximately 0.9% (w / v). In some embodiments, Exbumin® is present at approximately 0.1% (w / v) to approximately 0.8% (w / v). In some embodiments, Exbumin® is present at approximately 0.1% (w / v) to approximately 0.7% (w / v). In some embodiments, Exbumin® is present at approximately 0.1% (w / v) to approximately 0.6% (w / v). In some embodiments, Exbumin® is present at approximately 0.1% (w / v) to approximately 0.5% (w / v).In some embodiments, Exbumin® is present at approximately 0.1% (w / v) to approximately 0.4% (w / v). In some embodiments, Exbumin® is present at approximately 0.1% (w / v) to approximately 0.3% (w / v). In some embodiments, Exbumin® is present at approximately 0.1% (w / v) to approximately 0.2% (w / v).

[0196] In some embodiments, Exbumin® is present in concentrations of approximately 0.1% (w / v), 0.2% (w / v), 0.3% (w / v), 0.4% (w / v), 0.5% (w / v), 0.6% (w / v), 0.7% (w / v), 0.8% (w / v), 0.9% (w / v), 1% (w / v), 1.1% (w / v), 1.2% (w / v), 1.3% (w / v), and 1.4% (w / v). It is present in approximately 1.5% (w / v), 1.6% (w / v), 1.7% (w / v), 1.8% (w / v), 1.9% (w / v), 2% (w / v), 2.1% (w / v), 2.2% (w / v), 2.3% (w / v), 2.4% (w / v), 2.5% (w / v), 2.6% (w / v), 2.7% (w / v), 2.8% (w / v), 2.9% (w / v), or 3% (w / v).

[0197] In some embodiments, Exbumin® is present at approximately 0.1% (w / v). In some embodiments, Exbumin® is present at approximately 0.2% (w / v). In some embodiments, Exbumin® is present at approximately 0.3% (w / v). In some embodiments, Exbumin® is present at approximately 0.4% (w / v). In some embodiments, Exbumin® is present at approximately 0.5% (w / v). In some embodiments, Exbumin® is present at approximately 0.6% (w / v). In some embodiments, Exbumin® is present at approximately 0.7% (w / v). In some embodiments, Exbumin® is present at approximately 0.8% (w / v). In some embodiments, Exbumin® is present at approximately 0.9% (w / v). In some embodiments, Exbumin® is present at approximately 1% (w / v). In some embodiments, Exbumin® is present at approximately 1.1% (w / v). In some embodiments, Exbumin® is present at approximately 1.2% (w / v). In some embodiments, Exbumin® is present at approximately 1.3% (w / v). In some embodiments, Exbumin® is present at approximately 1.4% (w / v). In some embodiments, Exbumin® is present at approximately 1.5% (w / v). In some embodiments, Exbumin® is present at approximately 1.6% (w / v). In some embodiments, Exbumin® is present at approximately 1.7% (w / v). In some embodiments, Exbumin® is present at approximately 1.8% (w / v). In some embodiments, Exbumin® is present at approximately 1.9% (w / v). In some embodiments, Exbumin® is present at approximately 2.0% (w / v). In some embodiments, Exbumin® is present at approximately 2.1% (w / v). In some embodiments, Exbumin® is present at approximately 2.2% (w / v). In some embodiments, Exbumin® is present at approximately 2.3% (w / v).In some embodiments, Exbumin® is present at approximately 2.4% (w / v). In some embodiments, Exbumin® is present at approximately 2.5% (w / v). In some embodiments, Exbumin® is present at approximately 2.6% (w / v). In some embodiments, Exbumin® is present at approximately 2.7% (w / v). In some embodiments, Exbumin® is present at approximately 2.8% (w / v). In some embodiments, Exbumin® is present at approximately 2.9% (w / v). In some embodiments, Exbumin® is present at approximately 3.0% (w / v).

[0198] In some embodiments, Exbumin® is present at approximately 0.5% (w / v). In some embodiments, Exbumin® is present at approximately 1% (w / v).

[0199] In some embodiments, the protein excipient is non-recombinant human serum albumin. In some embodiments, the non-recombinant human serum albumin is any non-recombinant human serum albumin. In some embodiments, the non-recombinant human serum albumin is FDA-approved USP-grade non-recombinant human serum albumin. FDA-approved USP-grade non-recombinant human serum albumin can be obtained from any suitable private supplier, such as Nova, Octapharma, Grifols Bio Supplies, etc., without limitation.

[0200] In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 3% (w / v), or any value or range in between. In some embodiments, non-recombinant human serum albumin is present at approximately 0.2% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.3% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.4% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.5% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.6% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.7% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.8% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.9% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.2% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.4% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.5% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.6% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.8% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.2% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.4% (w / v) to approximately 3% (w / v).In some embodiments, non-recombinant human serum albumin is present at approximately 2.5% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.6% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.8% (w / v) to approximately 3% (w / v).

[0201] In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.8% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.6% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.5% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.4% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.2% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.0% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.8% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.6% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.5% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.4% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.2% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.0% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.9% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.8% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.7% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.6% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.5% (w / v).In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.4% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.2% (w / v).

[0202] In some embodiments, non-recombinant human serum albumin is present in concentrations of approximately 0.1% (w / v), 0.2% (w / v), 0.3% (w / v), 0.4% (w / v), 0.5% (w / v), 0.6% (w / v), 0.7% (w / v), 0.8% (w / v), 0.9% (w / v), 1% (w / v), 1.1% (w / v), 1.2% (w / v), 1.3% (w / v), and 1.4% (w / v). It is present in approximately 1.5% (w / v), 1.6% (w / v), 1.7% (w / v), 1.8% (w / v), 1.9% (w / v), 2% (w / v), 2.1% (w / v), 2.2% (w / v), 2.3% (w / v), 2.4% (w / v), 2.5% (w / v), 2.6% (w / v), 2.7% (w / v), 2.8% (w / v), 2.9% (w / v), or 3% (w / v).

[0203] In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.2% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.4% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.5% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.6% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.7% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.8% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.9% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.1% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.2% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.4% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.5% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.6% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.7% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.8% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.9% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.1% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.2% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.3% (w / v).In some embodiments, non-recombinant human serum albumin is present at approximately 2.4% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.5% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.6% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.7% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.8% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.9% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 3% (w / v).

[0204] In some embodiments, non-recombinant human serum albumin is present at approximately 0.5% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1% (w / v).

[0205] In various embodiments, the pharmaceutical composition comprises a lentiviral vector, a pharmaceutically acceptable buffer, a pharmaceutically acceptable salt, a sugar, and a protein excipient, wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0206] In various embodiments, the pharmaceutical composition comprises a lentiviral vector, a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 100 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 800 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0207] In various embodiments, the pharmaceutical composition comprises a lentiviral vector, a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 50 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 400 mM, a sugar in an amount of about 2% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 2% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0208] In various embodiments, the pharmaceutical composition comprises a lentiviral vector, a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 40 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 300 mM, a sugar in an amount of about 3% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 1% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0209] In various embodiments, the pharmaceutical composition comprises a lentiviral vector, a pharmaceutically acceptable buffer at a concentration of about 10 mM to about 30 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 200 mM, a sugar in an amount of about 3% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 1% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0210] In various embodiments, the pharmaceutical composition comprises a lentiviral vector, a pharmaceutically acceptable buffer at a concentration of about 10 mM to about 30 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 200 mM, a sugar in an amount of about 3% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 1% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5.

[0211] In various embodiments, the pharmaceutical composition comprises a lentiviral vector, a pharmaceutically acceptable buffer at a concentration of about 20 mM, a pharmaceutically acceptable salt at a concentration of about 150 mM, a sugar at a concentration of about 4% (w / v), and a protein excipient at a concentration of about 0.5% (w / v), wherein the pharmaceutical composition has a pH of about 7.0.

[0212] In some embodiments, the lentiviral vector is a pseudotyped lentiviral vector. Exemplary viral structural proteins that can be used for pseudotyping the lentiviral vectors provided herein can be found, at least, in WO2023 / 064884, WO2023 / 114698, WO2023 / 114884, WO2023 / 154858, and WO2024 / 026284, each of which is incorporated herein by reference in its entirety. In some embodiments, the lentiviral vector is a VSV-G pseudotyped lentivirus. In some embodiments, the VSV-G pseudotyped lentivirus is as provided herein.

[0213] In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of about 1.0E +05 ~1.0E +09 TU / mL.

[0214] In some embodiments, the VSV-G pseudotyped lentivirus is about 1.0E +05 ~ about 1.0E +09 TU / mL, about 1.0E +05 ~ about 1.0E +08 TU / mL, about 1.0E +05 ~ about 1.0E +07 TU / mL, about 1.0E +05 ~1.0E +06 TU / mL, about 1.0E +06 ~ about 1.0E +09 TU / mL, about 1.0E +06 ~ about 1.0E +08 TU / mL, about 1.0E +06 ~ about 1.0E +07 TU / mL, about 1.0E +07 ~ about 1.0E +09 TU / mL, about 1.0E +07 ~ about 1.0E +08 TU / mL, or about 1.0E +08 ~ about 1.0E +09 TU / mL.

[0215] In some embodiments, the VSV-G pseudotyped lentivirus is about 1.0E+05 ~Approximately 1.0E +09 It is present at a concentration of TU / mL. In some embodiments, the VSV-G pseudotyped lentivirus is approximately 1.0E +05 ~Approximately 1.0E +08 It is present at a concentration of TU / mL. In some embodiments, the VSV-G pseudotyped lentivirus is approximately 1.0E +05 ~Approximately 1.0E +07 It is present at a concentration of TU / mL. In some embodiments, the VSV-G pseudotyped lentivirus is approximately 1.0E +05 ~Approximately 1.0E +06 It is present at a concentration of TU / mL. In some embodiments, the VSV-G pseudotyped lentivirus is approximately 1.0E +06 ~Approximately 1.0E +09 It is present at a concentration of TU / mL. In some embodiments, the VSV-G pseudotyped lentivirus is approximately 1.0E +06 ~Approximately 1.0E +08 It is present at a concentration of TU / mL. In some embodiments, the VSV-G pseudotyped lentivirus is approximately 1.0E +06 ~Approximately 1.0E +07 It is present at a concentration of TU / mL. In some embodiments, the VSV-G pseudotyped lentivirus is approximately 1.0E +07 ~Approximately 1.0E +09 It is present at a concentration of TU / mL. In some embodiments, the VSV-G pseudotyped lentivirus is approximately 1.0E +07 ~Approximately 1.0E +08 It is present at a concentration of TU / mL. In some embodiments, the VSV-G pseudotyped lentivirus is approximately 1.0E +08 ~Approximately 1.0E +09 It exists at a concentration of TU / mL.

[0216] In some embodiments, the VSV-G pseudotyped lentivirus is at least 1.0E +05 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 2.0E. +05 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 3.0E. +05It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 4.0E. +05 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 5.0E. +05 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 6.0E. +05 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 7.0E. +05 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 8.0E. +05 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 9.0E. +05 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 1.0E. +06 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 2.0E. +06 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 3.0E. +06 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 4.0E. +06 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 5.0E. +06 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 6.0E. +06 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 7.0E. +06 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 8.0E. +06 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 9.0E. +06 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 1.0E. +07 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 2.0E. +07It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 3.0E. +07 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 4.0E. +07 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 5.0E. +07 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 6.0E. +07 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 7.0E. +07 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 8.0E. +07 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 9.0E. +07 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 1.0E. +08 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 2.0E. +08 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 3.0E. +08 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 4.0E. +08 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 5.0E. +08 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 6.0E. +08 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 7.0E. +08 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 8.0E. +08 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 9.0E. +08 It is present at a concentration of . In some embodiments, the VSV-G pseudotyped lentivirus is present at a concentration of at least 1.0E. +09It exists at this concentration.

[0217] In some embodiments, a pharmaceutical composition is provided which comprises a VSV-G pseudotyped lentivirus, about 10 mM to about 30 mM L-histidine, about 100 mM to about 400 mM sodium chloride, about 1% (w / v) to about 5% (w / v) sucrose, and about 0.1% (w / v) to about 3% (w / v) unrecombinant human serum albumin, and the pharmaceutical composition has a pH of about 5.5 to about 8.0.

[0218] In some embodiments, the VSV-G pseudotyped lentivirus is present at concentrations provided herein. In some embodiments, the VSV-G pseudotyped lentivirus is present at approximately 1.0E as provided herein. +05 ~Approximately 1.0E +09 It exists at this concentration.

[0219] In some embodiments, L-histidine is present at a concentration of about 10 mM to about 30 mM, or any value or range within that range. In some embodiments, L-histidine is present at a concentration of about 15 mM to about 30 mM. In some embodiments, L-histidine is present at a concentration of about 20 mM to about 30 mM. In some embodiments, L-histidine is present at a concentration of about 25 mM to about 30 mM. In some embodiments, L-histidine is present at a concentration of about 10 mM to about 25 mM. In some embodiments, L-histidine is present at a concentration of about 10 mM to about 20 mM. In some embodiments, L-histidine is present at a concentration of about 10 mM to about 15 mM.

[0220] In some embodiments, L-histidine is present at a concentration of about 10 mM. In some embodiments, L-histidine is present at a concentration of about 11 mM. In some embodiments, L-histidine is present at a concentration of about 12 mM. In some embodiments, L-histidine is present at a concentration of about 13 mM. In some embodiments, L-histidine is present at a concentration of about 14 mM. In some embodiments, L-histidine is present at a concentration of about 15 mM. In some embodiments, L-histidine is present at a concentration of about 16 mM. In some embodiments, L-histidine is present at a concentration of about 17 mM. In some embodiments, L-histidine is present at a concentration of about 18 mM. In some embodiments, L-histidine is present at a concentration of about 19 mM. In some embodiments, L-histidine is present at a concentration of about 20 mM. In some embodiments, L-histidine is present at a concentration of about 25 mM. In some embodiments, L-histidine is present at a concentration of about 30 mM.

[0221] In some embodiments, the pharmaceutical composition has a pH of about 5.5 to about 8, or any value or range within that range. In some embodiments, the pharmaceutical composition has a pH of about 6 to about 8. In some embodiments, the pharmaceutical composition has a pH of about 6.5 to about 8. In some embodiments, the pharmaceutical composition has a pH of about 7 to about 8. In some embodiments, the pharmaceutical composition has a pH of about 7.5 to about 8. In some embodiments, the pharmaceutical composition has a pH of about 6 to about 7.5. In some embodiments, the pharmaceutical composition has a pH of about 6 to about 7. In some embodiments, the pharmaceutical composition has a pH of about 6 to about 6.5.

[0222] In some embodiments, the pharmaceutical composition has a pH of about 6. In some embodiments, the pharmaceutical composition has a pH of about 6.5. In some embodiments, the pharmaceutical composition has a pH of about 7. In some embodiments, the pharmaceutical composition has a pH of about 7.5. In some embodiments, the pharmaceutical composition has a pH of about 8.

[0223] In some embodiments, L-histidine is present at a concentration of about 10 mM to about 25 mM, and the pharmaceutical composition has a pH of about 6 to about 7.

[0224] In some embodiments, L-histidine is present at approximately 14 mM, and the pharmaceutical composition has a pH of approximately 7.0.

[0225] In some embodiments, L-histidine is present at approximately 20 mM, and the pharmaceutical composition has a pH of approximately 7.0.

[0226] In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 400 mM, or any value or range within that range. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 390 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 380 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 370 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 360 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 350 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 340 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 330 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 320 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 310 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 300 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 290 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 280 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 270 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 260 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 250 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 240 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 230 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 220 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 210 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 200 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 190 mM.In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 180 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 170 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 160 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 150 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 140 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 130 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 120 mM. In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 110 mM.

[0227] In some embodiments, sodium chloride is present at a concentration of about 110 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 120 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 130 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 140 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 150 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 160 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 170 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 180 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 190 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 200 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 210 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 220 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 230 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 240 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 250 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 260 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 270 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 280 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 290 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 300 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 310 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 320 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 330 mM to about 400 mM.In some embodiments, sodium chloride is present at a concentration of about 340 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 350 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 360 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 370 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 380 mM to about 400 mM. In some embodiments, sodium chloride is present at a concentration of about 390 mM to about 400 mM.

[0228] In some embodiments, sodium chloride is present at a concentration of about 100 mM to about 200 mM. In some embodiments, sodium chloride is present at a concentration of about 125 mM to about 175 mM.

[0229] In some embodiments, sodium chloride is present at a concentration of about 100 mM. In some embodiments, sodium chloride is present at a concentration of about 110 mM. In some embodiments, sodium chloride is present at a concentration of about 120 mM. In some embodiments, sodium chloride is present at a concentration of about 125 mM. In some embodiments, sodium chloride is present at a concentration of about 130 mM. In some embodiments, sodium chloride is present at a concentration of about 140 mM. In some embodiments, sodium chloride is present at a concentration of about 150 mM. In some embodiments, sodium chloride is present at a concentration of about 160 mM. In some embodiments, sodium chloride is present at a concentration of about 170 mM. In some embodiments, sodium chloride is present at a concentration of about 175 mM. In some embodiments, sodium chloride is present at a concentration of about 180 mM. In some embodiments, sodium chloride is present at a concentration of about 190 mM. In some embodiments, sodium chloride is present at a concentration of about 200 mM.

[0230] In some embodiments, sodium chloride is present at a concentration of approximately 150 mM.

[0231] In some embodiments, sucrose is present in an amount of approximately 1%(w / v) to approximately 5%(w / v), or any value or range within that range. In some embodiments, sucrose is present in an amount of approximately 1%(w / v) to approximately 4%(w / v). In some embodiments, sucrose is present in an amount of approximately 1%(w / v) to approximately 3%(w / v). In some embodiments, sucrose is present in an amount of approximately 1%(w / v) to approximately 2%(w / v). In some embodiments, sucrose is present in an amount of approximately 2%(w / v) to approximately 5%(w / v). In some embodiments, sucrose is present in an amount of approximately 3%(w / v) to approximately 5%(w / v). In some embodiments, sucrose is present in an amount of approximately 4%(w / v) to approximately 5%(w / v). In some embodiments, sucrose is present in an amount of approximately 1%(w / v). In some embodiments, sucrose is present in an amount of approximately 2%(w / v). In some embodiments, sucrose is present at approximately 3% (w / v). In some embodiments, sucrose is present at approximately 4% (w / v). In some embodiments, sucrose is present at approximately 5% (w / v).

[0232] In some embodiments, sucrose is present at approximately 4% (w / v).

[0233] In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 3% (w / v), or any value or range in between. In some embodiments, non-recombinant human serum albumin is present at approximately 0.2% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.3% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.4% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.5% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.6% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.7% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.8% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.9% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.1% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.2% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.3% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.4% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.5% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.6% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.7% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.8% (w / v) to approximately 3% (w / v).In some embodiments, non-recombinant human serum albumin is present at approximately 1.9% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.1% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.2% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.3% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.4% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.5% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.6% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.7% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.8% (w / v) to approximately 3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.9% (w / v) to approximately 3% (w / v).

[0234] In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 3.0% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.9% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.8% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.7% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.6% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.5% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.4% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.2% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.1% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 2.0% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.9% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.8% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.7% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.6% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.5% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.4% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.3% (w / v).In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.2% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.1% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 1.0% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.9% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.8% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.7% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.6% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.5% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.4% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v) to approximately 0.2% (w / v).

[0235] In some embodiments, non-recombinant human serum albumin is present in concentrations of approximately 0.1% (w / v), 0.2% (w / v), 0.3% (w / v), 0.4% (w / v), 0.5% (w / v), 0.6% (w / v), 0.7% (w / v), 0.8% (w / v), 0.9% (w / v), 1% (w / v), 1.1% (w / v), 1.2% (w / v), 1.3% (w / v), and 1.4% (w / v). It is present in approximately 1.5% (w / v), 1.6% (w / v), 1.7% (w / v), 1.8% (w / v), 1.9% (w / v), 2% (w / v), 2.1% (w / v), 2.2% (w / v), 2.3% (w / v), 2.4% (w / v), 2.5% (w / v), 2.6% (w / v), 2.7% (w / v), 2.8% (w / v), 2.9% (w / v), or 3% (w / v).

[0236] In some embodiments, non-recombinant human serum albumin is present at approximately 0.1% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.2% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.4% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.5% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.6% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.7% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.8% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 0.9% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.1% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.2% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.3% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.4% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.5% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.6% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.7% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.8% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1.9% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.1% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.2% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.3% (w / v).In some embodiments, non-recombinant human serum albumin is present at approximately 2.4% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.5% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.6% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.7% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.8% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 2.9% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 3% (w / v).

[0237] In some embodiments, non-recombinant human serum albumin is present at approximately 0.5% (w / v). In some embodiments, non-recombinant human serum albumin is present at approximately 1% (w / v).

[0238]

[0239] In some embodiments, the lentiviral vector is a VSV-G pseudotyped lentivirus. In some embodiments, the VSV-G pseudotyped lentivirus is as provided herein. In some embodiments, the VSV-G pseudotyped lentivirus comprises a VSV-G polypeptide containing a mutation corresponding to the mutation at position 182 of SEQ ID NO: 2, as provided herein. In some embodiments, the VSV-G pseudotyped lentivirus comprises a VSV-G polypeptide containing mutations corresponding to the mutations at positions 182, 214, and / or 352 of SEQ ID NO: 2, as provided herein. In some embodiments, the mutation at position 182 is as provided herein. In some embodiments, the mutation at position 182 is 182A, as provided herein. In some embodiments, the mutation at position 182 is 182E, as provided herein. In some embodiments, the mutation at position 182 is 182D, as provided herein. In some embodiments, the mutation at position 214 is as provided herein. In some embodiments, the mutation at position 214 is 214N, as provided herein. In some embodiments, the mutation at position 352 is as provided herein. In some embodiments, the mutation at position 352 is 352A, as provided herein.

[0240] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus containing a VSV-G polypeptide with mutations corresponding to the mutations at positions 182, 214, and / or 352 of SEQ ID NO: 2, an L-histidine buffer at a concentration of about 10 mM to about 30 mM, sodium chloride at a concentration of about 100 mM to about 400 mM, sucrose in an amount of about 1% (w / v) to about 5% (w / v), and unrecombinant human serum albumin in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5. In some embodiments, the unrecombinant human serum albumin is as provided herein.

[0241] In some embodiments, a pharmaceutical composition is provided which comprises a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide containing mutations corresponding to the mutations at positions 182, 214, and / or 352 of SEQ ID NO: 2, wherein the mutation at position 182 comprises a VSV-G polypeptide containing 182A, 182E, or 182D; L-histidine buffer at a concentration of about 10 mM to about 30 mM; sodium chloride at a concentration of about 100 mM to about 400 mM; sucrose in an amount of about 1% (w / v) to about 5% (w / v); and unrecombinant human serum albumin in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5. In some embodiments, the unrecombinant human serum albumin is as provided herein.

[0242] In some embodiments, a pharmaceutical composition is provided which comprises a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide containing mutations corresponding to the mutations at positions 182, 214, and / or 352 of SEQ ID NO: 2, wherein the mutation at position 182 comprises a VSV-G polypeptide containing a VSV-G polypeptide corresponding to 182E; L-histidine buffer at a concentration of about 10 mM to about 30 mM; sodium chloride at a concentration of about 100 mM to about 400 mM; sucrose in an amount of about 1% (w / v) to about 5% (w / v); and unrecombinant human serum albumin in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5. In some embodiments, the unrecombinant human serum albumin is as provided herein.

[0243] In some embodiments, a pharmaceutical composition is provided which comprises a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide containing mutations corresponding to the mutations at positions 182, 214, and / or 352 of SEQ ID NO: 2, wherein the mutation at position 182 comprises a VSV-G polypeptide containing a VSV-G polypeptide corresponding to 182D; L-histidine buffer at a concentration of about 10 mM to about 30 mM; sodium chloride at a concentration of about 100 mM to about 400 mM; sucrose in an amount of about 1% (w / v) to about 5% (w / v); and unrecombinant human serum albumin in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5. In some embodiments, the unrecombinant human serum albumin is as provided herein.

[0244] In some embodiments, a pharmaceutical composition is provided which comprises a VSV-G pseudotyped lentivirus containing a VSV-G polypeptide with mutations I182E, T214N, and / or T352A compared to SEQ ID NO: 2, an L-histidine buffer at a concentration of about 10 mM to about 30 mM, sodium chloride at a concentration of about 100 mM to about 400 mM, sucrose in an amount of about 1% (w / v) to about 5% (w / v), and unrecombinant human serum albumin in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5. In some embodiments, the unrecombinant human serum albumin is as provided herein.

[0245] In some embodiments, a pharmaceutical composition is provided which comprises a VSV-G pseudotyped lentivirus containing a VSV-G polypeptide with mutations I182E, T214N, and T352A compared to SEQ ID NO: 2, an L-histidine buffer at a concentration of about 10 mM to about 30 mM, sodium chloride at a concentration of about 100 mM to about 400 mM, sucrose in an amount of about 1% (w / v) to about 5% (w / v), and unrecombinant human serum albumin in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5. In some embodiments, the unrecombinant human serum albumin is as provided herein.

[0246] In some embodiments, a pharmaceutical composition is provided which comprises a VSV-G pseudotyped lentivirus containing a VSV-G polypeptide with mutations I182D, T214N, and / or T352A compared to SEQ ID NO: 2, an L-histidine buffer at a concentration of about 10 mM to about 30 mM, sodium chloride at a concentration of about 100 mM to about 400 mM, sucrose in an amount of about 1% (w / v) to about 5% (w / v), and unrecombinant human serum albumin in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5. In some embodiments, the unrecombinant human serum albumin is as provided herein.

[0247] In some embodiments, a pharmaceutical composition is provided which comprises a VSV-G pseudotyped lentivirus containing a VSV-G polypeptide with mutations I182D, T214N, and T352A compared to SEQ ID NO: 2, an L-histidine buffer at a concentration of about 10 mM to about 30 mM, sodium chloride at a concentration of about 100 mM to about 400 mM, sucrose in an amount of about 1% (w / v) to about 5% (w / v), and unrecombinant human serum albumin in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5. In some embodiments, the unrecombinant human serum albumin is as provided herein.

[0248] In some embodiments, a pharmaceutical composition is provided which comprises a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, or SEQ ID NO: 25; a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 100 mM; a pharmaceutically acceptable salt at a concentration of about 100 mM to about 800 mM; a sugar in an amount of about 1% (w / v) to about 5% (w / v); and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0249] In some embodiments, a pharmaceutical composition is provided which comprises a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, or SEQ ID NO: 25; a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 50 mM; a pharmaceutically acceptable salt at a concentration of about 100 mM to about 400 mM; a sugar in an amount of about 1% (w / v) to about 5% (w / v); and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0250] In some embodiments, a pharmaceutical composition is provided which comprises a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, or SEQ ID NO: 25; a pharmaceutically acceptable buffer at a concentration of about 10 mM to about 30 mM; a pharmaceutically acceptable salt at a concentration of about 100 mM to about 400 mM; a sugar in an amount of about 1% (w / v) to about 5% (w / v); and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5.

[0251] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, or SEQ ID NO: 25; L-histidine buffer at a concentration of about 10 mM to about 30 mM; sodium chloride at a concentration of about 100 mM to about 400 mM; sucrose in an amount of about 1% (w / v) to about 5% (w / v); and unrecombinant human serum albumin in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5. In some embodiments, the unrecombinant human serum albumin is as provided herein.

[0252] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 22, a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 100 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 800 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0253] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 22, a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 50 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 400 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0254] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 22, a pharmaceutically acceptable buffer at a concentration of about 10 mM to about 30 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 400 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5.

[0255] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 22, an L-histidine buffer at a concentration of about 10 mM to about 30 mM, sodium chloride at a concentration of about 100 mM to about 400 mM, sucrose in an amount of about 1% (w / v) to about 5% (w / v), and unrecombinant human serum albumin in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5. In some embodiments, the unrecombinant human serum albumin is as provided herein.

[0256] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 23, a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 100 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 800 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0257] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 23, a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 50 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 400 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0258] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 23, a pharmaceutically acceptable buffer at a concentration of about 10 mM to about 30 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 400 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5.

[0259] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 23, an L-histidine buffer at a concentration of about 10 mM to about 30 mM, sodium chloride at a concentration of about 100 mM to about 400 mM, sucrose in an amount of about 1% (w / v) to about 5% (w / v), and unrecombinant human serum albumin in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5. In some embodiments, the unrecombinant human serum albumin is as provided herein.

[0260] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 24, a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 100 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 800 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0261] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 24, a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 50 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 400 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0262] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 24, a pharmaceutically acceptable buffer at a concentration of about 10 mM to about 30 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 400 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5.

[0263] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 24, an L-histidine buffer at a concentration of about 10 mM to about 30 mM, sodium chloride at a concentration of about 100 mM to about 400 mM, sucrose in an amount of about 1% (w / v) to about 5% (w / v), and unrecombinant human serum albumin in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5. In some embodiments, the unrecombinant human serum albumin is as provided herein.

[0264] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 25, a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 100 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 800 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0265] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 25, a pharmaceutically acceptable buffer at a concentration of about 5 mM to about 50 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 400 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.0 to about 8.0.

[0266] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 25, a pharmaceutically acceptable buffer at a concentration of about 10 mM to about 30 mM, a pharmaceutically acceptable salt at a concentration of about 100 mM to about 400 mM, a sugar in an amount of about 1% (w / v) to about 5% (w / v), and a protein excipient in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5.

[0267] In some embodiments, a pharmaceutical composition is provided, comprising a VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide having the amino acid sequence of SEQ ID NO: 25, an L-histidine buffer at a concentration of about 10 mM to about 30 mM, sodium chloride at a concentration of about 100 mM to about 400 mM, sucrose in an amount of about 1% (w / v) to about 5% (w / v), and unrecombinant human serum albumin in an amount of about 0.1% (w / v) to about 3% (w / v), wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5. In some embodiments, the unrecombinant human serum albumin is as provided herein.

[0268] As provided herein, pharmaceutical compositions may have a pH of about 5.5 to about 8.0, or about 6.0 to about 8.0, or any value or range in between. The compositions may have a pharmaceutically acceptable buffer, such as those provided herein, to maintain the pH. When preparing a composition, the pH of the composition may be adjusted to a selected pH by adding an acid or base, as necessary. For example, in some embodiments, the pH may be made more acidic by adding HCl or another suitable acid, and the pH may be made more basic by adding NaOH or another suitable base, so that the composition may have a final pH of about 5.5 to about 8.0, or about 6.0 to about 8.0, or any value or range in between, as provided herein. Suitable acids are known in the art and include, but are not limited to, hydrochloric acid (HCl), acetic acid (C2H4O2), and sulfuric acid (H2SO4). Suitable bases are known in the art and include, but are not limited to, sodium hydroxide (NaOH), potassium hydroxide (KOH), trisodium phosphate (Na3PO4), potassium carbonate (K2CO3), and sodium carbonate (Na2CO3). The acids and bases provided herein are merely illustrative and are not intended to limit them in any way. Suitable acids and bases are known in the art, and any such acid or base is within the scope of this disclosure. In some embodiments, the acid is hydrochloric acid. In some embodiments, the base is sodium hydroxide.

[0269] Viral vector In some embodiments, the lentiviral vector of the Disclosure is a pseudotyped viral vector. In some embodiments, the pseudotyped viral vector is a VSV-G pseudotyped lentivirus. In some embodiments, the VSV-G pseudotyped lentivirus comprises a VSV-G polypeptide or protein.

[0270] In some embodiments, the VSV-G pseudotyped lentivirus contains a VSV-G protein with a mutation at position 198 compared to SEQ ID NO: 1, or at position 182 compared to SEQ ID NO: 2. SEQ ID NO: 1 is the full-length protein, and SEQ ID NO: 2 is the ectodomain of the VSV-G protein. The 16-mer signal peptide MKCLLYLAFLFIGVNC (SEQ ID NO: 65), shown at the N-terminus of SEQ ID NO: 1, is cleaved, leaving the protein of SEQ ID NO: 2 intact. Thus, the mutation can be specified for SEQ ID NO: 2, but naturally, it can also be specified for SEQ ID NO: 1. SEQ ID NO: 1 contains this leader sequence and therefore has a position number 16 more than the position shown for SEQ ID NO: 2. In some embodiments, this mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the I182D mutation compared to SEQ ID NO: 2. In some embodiments, the mutation is the I182E mutation compared to SEQ ID NO: 2.

[0271] In some embodiments, the VSV-G pseudotyped lentivirus contains a VSV-G protein with a mutation at position 198 compared to SEQ ID NO: 10, or at position 182 compared to SEQ ID NO: 11. SEQ ID NO: 10 is the full-length protein, and SEQ ID NO: 11 is the ectodomain of the VSV-G protein. The 16-mer signal peptide MLSYLIFALVVSPILG (SEQ ID NO: 66), shown at the N-terminus of SEQ ID NO: 10, is cleaved leaving the protein of SEQ ID NO: 11 intact. Thus, the mutation can be specified for SEQ ID NO: 11, but naturally, it can also be specified for SEQ ID NO: 10. SEQ ID NO: 10 contains this leader sequence and therefore has a position number 16 more than the position shown for SEQ ID NO: 11. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the T182D mutation compared to SEQ ID NO: 11. In some embodiments, the mutation is the T182E mutation compared to SEQ ID NO: 11.

[0272] In some embodiments, the VSV-G pseudotyped lentivirus contains a VSV-G protein with a mutation at position 198 compared to SEQ ID NO: 12, or at position 182 compared to SEQ ID NO: 13. SEQ ID NO: 12 is the full-length protein, and SEQ ID NO: 13 is the ectodomain of the VSV-G protein. The 16-mer signal peptide MLRLFLFCFLALGAHS (SEQ ID NO: 67), shown at the N-terminus of SEQ ID NO: 12, is cleaved leaving the protein of SEQ ID NO: 13 intact. Thus, the mutation can be specified for SEQ ID NO: 13, but naturally, it can also be specified for SEQ ID NO: 12. SEQ ID NO: 12 contains this leader sequence and therefore has a position number 16 more than the position shown for SEQ ID NO: 13. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the A182D mutation compared to SEQ ID NO: 13. In some embodiments, the mutation is the A182E mutation compared to SEQ ID NO: 13.

[0273] In some embodiments, the VSV-G pseudotyped lentivirus contains a VSV-G protein with a mutation at position 203 compared to SEQ ID NO: 14, or at position 182 compared to SEQ ID NO: 15. SEQ ID NO: 14 is the full-length protein, and SEQ ID NO: 15 is the ectodomain of the VSV-G protein. The 21-mer signal peptide MKMKMVIAGLILCIGILPAIG (SEQ ID NO: 68), shown at the N-terminus of SEQ ID NO: 14, is cleaved leaving the protein of SEQ ID NO: 15 intact. Thus, the mutation can be specified for SEQ ID NO: 15, but naturally, it can also be specified for SEQ ID NO: 14. SEQ ID NO: 14 contains this leader sequence and therefore has a position number 21 more than the position shown for SEQ ID NO: 15. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the V182D mutation compared to SEQ ID NO: 15. In some embodiments, the mutation is the V182E mutation compared to SEQ ID NO: 15.

[0274] In some embodiments, the VSV-G pseudotyped lentivirus contains a VSV-G protein with a mutation at position 199 compared to SEQ ID NO: 16, or at position 182 compared to SEQ ID NO: 17. SEQ ID NO: 16 is the full-length protein, and SEQ ID NO: 17 is the ectodomain of the VSV-G protein. The 17-mer signal peptide MTPAFILCMLLAGSSWA (SEQ ID NO: 69), shown at the N-terminus of SEQ ID NO: 16, is cleaved leaving the protein of SEQ ID NO: 17 intact. Therefore, the mutation can be specified for SEQ ID NO: 17, but naturally, it can also be specified for SEQ ID NO: 16. SEQ ID NO: 16 contains this leader sequence and therefore has a position number 17 more than the position shown for SEQ ID NO: 17. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the V182D mutation compared to SEQ ID NO: 17. In some embodiments, the mutation is the V182E mutation compared to SEQ ID NO: 17.

[0275] In some embodiments, the VSV-G pseudotyped lentivirus contains a VSV-G protein with a mutation at position 199 compared to SEQ ID NO: 18, or at position 182 compared to SEQ ID NO: 19. SEQ ID NO: 18 is the full-length protein, and SEQ ID NO: 19 is the ectodomain of the VSV-G protein. The 17-mer signal peptide MNFLLLTFIVLPLCSHA (SEQ ID NO: 70), shown at the N-terminus of SEQ ID NO: 18, is cleaved leaving the protein of SEQ ID NO: 19 intact. Therefore, the mutation can be specified for SEQ ID NO: 19, but naturally, it can also be specified for SEQ ID NO: 18. SEQ ID NO: 18 contains this leader sequence and therefore has a position number 17 positions higher than the position shown for SEQ ID NO: 19. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the V182D mutation compared to SEQ ID NO: 19. In some embodiments, the mutation is the V182E mutation compared to SEQ ID NO: 19.

[0276] In some embodiments, the VSV-G pseudotyped lentivirus contains a VSV-G protein with a mutation at position 199 compared to SEQ ID NO: 20, or at position 182 compared to SEQ ID NO: 21. SEQ ID NO: 20 is the full-length protein, and SEQ ID NO: 21 is the ectodomain of the VSV-G protein. The 17-mer signal peptide MLVLYLLLSLLALGAQC (SEQ ID NO: 71), shown at the N-terminus of SEQ ID NO: 20, is cleaved, leaving the protein of SEQ ID NO: 21 intact. Thus, the mutation can be specified for SEQ ID NO: 21, but naturally, it can also be specified for SEQ ID NO: 20. SEQ ID NO: 20 contains this leader sequence and therefore has a position number 17 positions higher than the position shown for SEQ ID NO: 21. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the I182D mutation compared to SEQ ID NO: 21. In some embodiments, the mutation is the I182E mutation compared to SEQ ID NO: 21.

[0277] Where used herein, when a protein or polypeptide is said to have mutations compared to a reference sequence, such a comparison is based on alignment, such as using BlastP, ClustalW, or ClutalOmega alignment software with default parameters. For example, position 182 can be found in SEQ ID NO: 2, and further, it can be found in comparison to other strains, as shown in Figure 3. Figure 3 shows clustal alignments of wild-type sequences of the ectodomains of various strains of the VSV-G protein. The residues in bold and underlined are the residues aligned to position 182 of SEQ ID NO: 2 in various strains. SEQ ID NO: 2 refers to the ectodomain of the VSV-G protein from the Indiana strain. SEQ ID NO: 11 refers to the ectodomain of the VSV-G protein from the New Jersey strain. SEQ ID NO: 13 refers to the ectodomain of the VSV-G protein from the Marraba strain. SEQ ID NO: 15 refers to the ectodomain of the VSV-G protein from the Carajas strain. SEQ ID NO: 17 refers to the extracellular domain of the VSV-G protein from the Alagoa strain. Sequence ID 19 refers to the ectodomain of the VSV-G protein of the Cocal strain. Sequence ID 21 refers to the ectodomain of the VSV-G protein of the Morreton strain. Therefore, the residue aligned at residue 182 compared to Sequence ID 2 can also be mutated as provided herein.

[0278] In some embodiments, the mutation at position 182 compared to SEQ ID NO: 2 is not alanine. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 2 is not valine.

[0279] In some embodiments, the mutation at position 182 compared to sequence number 2 is I182S, I182H, I182T, I182Q, or I182N. In some embodiments, the mutation at position 182 compared to sequence number 11 is T182S, T182H, T182Q, or T182N. In some embodiments, the mutation at position 182 compared to sequence number 13 is A182S, A182H, A182T, A182Q, or A182N. In some embodiments, the mutation at position 182 compared to sequence number 15 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 compared to sequence number 17 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 19 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 21 is I182S, I182H, I182T, I182Q, or I182N. In some embodiments, the mutation at position 182 is not a hydrophobic residue. In some embodiments, the mutation at position 182 is a charged residue. In some embodiments, the mutation at position 182 is a negatively charged residue.

[0280] Mutations may be described with reference to SEQ ID NO: 1 or SEQ ID NO: 2, which are VSV-G proteins derived from the Indiana strain, but mutations can also be used in other strains of the VSV-G protein. For example, mutations can be induced in the New Jersey, Marraba, Carajas, Alagoa, Cocal, or Morreton strains of VSV-G. In some embodiments, the respective sequences are as shown herein. Examples of these can be found, for example, in U.S. Patent Application Publication No. 20200216502, which is incorporated herein by reference. For example, the wild-type full-length or ectodomain of the VSV-G New Jersey strain is sequence number 10 and sequence number 11, respectively; the wild-type full-length or ectodomain of the VSV-G Marraba strain is sequence number 12 and sequence number 13, respectively; the wild-type full-length or ectodomain of the VSV-G Carajas strain is sequence number 14 and sequence number 15, respectively; the wild-type full-length or ectodomain of the VSV-G Alagoa strain is sequence number 16 and sequence number 17, respectively; the wild-type full-length or ectodomain of the VSV-G Cocal strain is sequence number 18 and sequence number 19, respectively; or the wild-type full-length or ectodomain of the VSV-G Morreton strain is sequence number 20 and sequence number 21, respectively.

[0281] Compared to SEQ ID NO: 2, a VSV-G protein containing a mutation at position 182 may also contain other mutations, such as those described in U.S. Patent Application Publication No. 20200216502 (which is incorporated herein by reference in its entirety). For example, a VSV-G protein may contain mutations at positions 8, 47, 209, and / or 354 of SEQ ID NO: 2.

[0282] In some embodiments, the substitution at position 8 is by any amino acid different from the amino acid at that position in the sequence of SEQ ID NO: 2, except for Y. In some embodiments, the substitution at position 209 is by any amino acid different from the amino acid at that position in the sequence of SEQ ID NO: 2, except for H. In some embodiments, the substitution at position 47 is by any amino acid different from the amino acid at that position in the sequence of SEQ ID NO: 2, except for K or R. In some embodiments, the substitution at position 354 is by any amino acid different from the amino acid at that position in the sequence of SEQ ID NO: 2, except for K or R.

[0283] In some embodiments, the substitution is a substitution of A, G, F, or Q at position 47 or 354, or both positions 47 and 354. In some embodiments, the substitution is A or Q.

[0284] In some embodiments, the substitution at position 8 is alanine, i.e., H8A.

[0285] In some embodiments, the substitution at position 47 is Q or N, i.e., K47Q or K47N.

[0286] In some embodiments, the protein contains a mutation (substitution) at position 10. In some embodiments, the substitution / mutation is Q10A, Q10R, or Q10K.

[0287] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 2 is at least, or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 2 (or SEQ ID NO: 1 if a full-length protein is used). In some embodiments, the polypeptide contains the I182D or I182E mutation. In some embodiments, the VSV-G protein contains the I182S, I182H, I182T, I182Q, or I182N mutation.

[0288] In some embodiments, a protein containing a mutation at position 182 is at least, or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 11 (or SEQ ID NO: 10 if a full-length protein is used). In some embodiments, the polypeptide contains the T182D or T182E mutation. In some embodiments, the VSV-G protein contains the T182S, T182H, T182Q, or T182N mutation.

[0289] In some embodiments, a protein containing a mutation at position 182 is at least, or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 13 (or SEQ ID NO: 12 if using a full-length protein). In some embodiments, the polypeptide contains the A182D or A182E mutation. In some embodiments, the VSV-G protein contains the A182S, A182H, A182T, A182Q, or A182N mutation.

[0290] In some embodiments, a protein containing a mutation at position 182 is at least, or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 15 (or SEQ ID NO: 14 if using a full-length protein). In some embodiments, the polypeptide contains the V182D or V182E mutation. In some embodiments, the VSV-G protein contains the V182S, V182H, V182T, V182Q, or V182N mutation.

[0291] In some embodiments, a protein containing a mutation at position 182 is at least, or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 17 (or SEQ ID NO: 16 if using a full-length protein) when a mutation at position 182 is present. In some embodiments, the polypeptide contains the V182D or V182E mutation. In some embodiments, the VSV-G protein contains the V182S, V182H, V182T, V182Q, or V182N mutation.

[0292] In some embodiments, a protein containing a mutation at position 182 is at least, or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 19 (or SEQ ID NO: 18 if using a full-length protein). In some embodiments, the polypeptide contains the V182D or V182E mutation. In some embodiments, the VSV-G protein contains the V182S, V182H, V182T, V182Q, or V182N mutation.

[0293] In some embodiments, a protein containing a mutation at position 182 is at least, or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 21 (or SEQ ID NO: 20 if a full-length protein is used). In some embodiments, the polypeptide contains the I182D or I182E mutation. In some embodiments, the VSV-G protein contains the I182S, I182H, I182T, I182Q, or I182N mutation.

[0294] Viral glycoproteins The mutant VSV-G protein can be used, for example, to pseudotype viruses such as lentiviruses, without limitation. Accordingly, in some embodiments, a viral vector comprising the mutant VSV-G protein provided herein is provided. In some embodiments, the viral vector comprises a VSV-G protein having a mutation at position 198 compared to SEQ ID NO: 1. In some embodiments, a protein having a mutation at position 182 compared to SEQ ID NO: 2 is at least, or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 2 (or SEQ ID NO: 1 if a full-length protein is used) with the mutation at position 182. In some embodiments, the polypeptide contains the I182D or I182E mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein contains the I182S, I182H, I182T, I182Q, or I182N mutation.

[0295] In some embodiments, the viral vector contains a VSV-G protein with a mutation at position 198 compared to SEQ ID NO: 10. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 11 contains a mutation at position 182 and is at least, or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 11 (or SEQ ID NO: 10 if a full-length protein is used). In some embodiments, the polypeptide contains the T182D or T182E mutation compared to SEQ ID NO: 11. In some embodiments, the VSV-G protein contains mutations in T182S, T182H, T182Q, or T182N.

[0296] In some embodiments, the viral vector contains a VSV-G protein with a mutation at position 198 compared to SEQ ID NO: 12. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 13 contains a mutation at position 182 and is at least, or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical compared to SEQ ID NO: 13 (or SEQ ID NO: 12 if a full-length protein is used). In some embodiments, the polypeptide contains the A182D or A182E mutation compared to SEQ ID NO: 13. In some embodiments, the VSV-G protein includes mutations in A182S, A182H, A182T, A182Q, or A182N.

[0297] In some embodiments, the viral vector contains a VSV-G protein with a mutation at position 203 compared to SEQ ID NO: 14. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 15 contains a mutation at position 182 and is at least, or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical compared to SEQ ID NO: 15 (or SEQ ID NO: 14 if a full-length protein is used). In some embodiments, the polypeptide contains the V182D or V182E mutation compared to SEQ ID NO: 15. In some embodiments, the VSV-G protein includes mutations in V182S, V182H, V182T, V182Q, or V182N.

[0298] In some embodiments, the viral vector contains a VSV-G protein with a mutation at position 199 compared to SEQ ID NO: 16. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 17 contains a mutation at position 182 and is at least, or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical compared to SEQ ID NO: 17 (or SEQ ID NO: 16 if a full-length protein is used). In some embodiments, the polypeptide contains the V182D or V182E mutation compared to SEQ ID NO: 17. In some embodiments, the VSV-G protein includes mutations in V182S, V182H, V182T, V182Q, or V182N.

[0299] In some embodiments, the viral vector contains a VSV-G protein with a mutation at position 199 compared to SEQ ID NO: 18. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 19 contains a mutation at position 182 and is at least, or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical compared to SEQ ID NO: 19 (or SEQ ID NO: 18 if a full-length protein is used). In some embodiments, the polypeptide contains the V182D or V182E mutation compared to SEQ ID NO: 19. In some embodiments, the VSV-G protein includes mutations in V182S, V182H, V182T, V182Q, or V182N.

[0300] In some embodiments, the viral vector contains a VSV-G protein with a mutation at position 199 compared to SEQ ID NO: 20. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 21 contains a mutation at position 182 and is at least, or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical compared to SEQ ID NO: 21 (or SEQ ID NO: 20 if a full-length protein is used). In some embodiments, the polypeptide contains the I182D or I182E mutation compared to SEQ ID NO: 21. In some embodiments, the VSV-G protein contains mutations in I182S, I182H, I182T, I182Q, or I182N.

[0301] In some embodiments, the VSV-G protein further includes mutations at positions corresponding to positions 214 and / or 352 of SEQ ID NO: 2. In some embodiments, the residue corresponding to position 214 of SEQ ID NO: 2 is T214. In some embodiments, the residue corresponding to position 352 of SEQ ID NO: 2 is T352. In some embodiments, the VSV-G protein includes a mutation corresponding to the T214N mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein includes a mutation corresponding to the T352A mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein includes the T214N and T352A mutations compared to SEQ ID NO: 2. These mutations can be combined with any other mutations provided herein. In some embodiments, the T214N and / or T352A mutations are combined with the I182E or I182D mutations. In some embodiments, the VSV-G protein contains the amino acid sequences of SEQ ID NOs. 22 and 23, which combine I182D or I182E with the T214N and T352A mutations, respectively. Such sequences, along with the leader sequences removed during protein processing, are shown below. VSV-G protein mutations I196D, T230N, and T368A (including leader sequences and adjusted numbering) MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQS CGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKD LFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(Sequence ID 24) VSV-G protein mutations I182D, T214N, and T352A (excluding the leader sequence) KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAV IVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFP ECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(Sequence ID 22) VSV-G protein containing mutations I196E, T230N, and T368A (including leader sequence and adjusted numbering) MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQS CGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKD LFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(Sequence ID 25) VSV-G protein containing mutations I182E, T214N, and T352A (without leader sequence) KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAV IVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFP ECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(Sequence ID 23)

[0302] In some embodiments, the VSV-G protein, compared to SEQ ID NO: 2, includes a mutation at position 182, and further includes mutations at position 38 and / or 320 or the position corresponding to SEQ ID NO: 2. In some embodiments, the residue corresponding to position 38 of SEQ ID NO: 2 is T38. In some embodiments, the residue corresponding to position 320 of SEQ ID NO: 2 is T320. In some embodiments, the VSV-G protein includes a mutation corresponding to the T38A mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein includes a mutation corresponding to the T320A mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein includes the T38A and T320A mutations compared to SEQ ID NO: 2. These mutations can be combined with any other mutations provided herein.

[0303] In some embodiments, other strains of the VSV-G protein described herein may further include one or more mutations corresponding to any of the other mutations, as provided herein, compared to SEQ ID NO: 2. For example, other strains of the VSV-G protein described herein may also include mutations corresponding to T38A, T214N, T320A, and / or T352A of SEQ ID NO: 2. In some embodiments, other strains of the VSV-G protein described herein may also include mutations corresponding to T214N and / or T352A of SEQ ID NO: 2, as shown in SEQ ID NOs. 22 and SEQ ID NOs. 23.

[0304] In some embodiments, the composition includes mutations described in Hwang et al., Gene Ther 2013 Aug;20(8):807-15. (Epub 2013 Jan 31) (which is incorporated herein by reference in its entirety). For example, mutations may be at positions 230, 368, 66, and / or 162, corresponding to SEQ ID NO: 1. These positions are 16 fewer than SEQ ID NO: 2 when the leader sequence is removed. In some embodiments, mutations at these positions are, for example, T230N, T368A, K66T, S162T, or any combination thereof. In some embodiments, the VSV-G protein includes the T230N and T368A mutations. In some embodiments, the VSV-G polypeptide includes K66T, S162T, T230N, and T368A. These positions correspond to positions in the full-length protein (SEQ ID NO: 1). In some embodiments, the VSV-G protein includes the T230N mutation, the T368A mutation, the K66T mutation, the S162T mutation, or any combination thereof. In some embodiments, the VSV-G protein further includes one or more mutations in addition to the mutation corresponding to position 182 of SEQ ID NO: 2, such as that described in U.S. Patent Application Publication No. 20200216502 (which is incorporated herein by reference in its entirety). For example, the VSV-G protein may further include mutations at positions 8, 47, 209, and / or 354 of SEQ ID NO: 2.

[0305] In some embodiments, the substitution at position 8 is by any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for Y. In some embodiments, the substitution at position 209 is by any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for H. In some embodiments, the substitution at position 47 is by any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for K or R. In some embodiments, the substitution at position 354 is by any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for K or R. In some embodiments, the substitution at position 47 or 354, or both positions 47 and 354, is substituted by A, G, F, or Q. In some embodiments, the substitution is A or Q. In some embodiments, the substitution at position 8 is alanine, i.e., H8A. In some embodiments, the substitution at position 47 is Q or N, i.e., K47Q or K47N. In some embodiments, the protein contains a mutation (substitution) at position 10. In some embodiments, the substitution / mutation is Q10A, Q10R, or Q10K.

[0306] Furthermore, in some embodiments, the virus can be pseudotyped with other viral structural proteins instead of the VSV-G protein or its variants. Preferred examples of other viral structural proteins can be found in at least WO2023 / 064884, WO2023 / 114698, WO2023 / 114884, and WO2023 / 154858, each of which is incorporated as a whole by reference.

[0307] Targeting part In some embodiments, the viral vector includes a target-directing moiety. The target-directing moiety can be used to target the viral vector containing the mutant VSV-G protein to cells expressing the target to which the target-directing moiety binds. In some embodiments, the target-directing moiety is an antibody, scFv antibody, antigen-binding domain, an ankyrin repeat (e.g., DARPIN), VHH domain antibody, nanobody, single-domain antibody, FN3 domain, or any combination thereof. The target-directing moiety can be bound to the viral surface via the Fc stalk of IgG. In some embodiments, the stalk includes a transmembrane domain. In some embodiments, the transmembrane domain includes a CD28 transmembrane domain. In some embodiments, the target-directing moiety is bound (fused or ligated) to the envelope glycoprotein G or H of a paramyxoviridae virus (e.g., morbillivirus such as measles virus, or henipavirus such as nipah virus, cedarvirus, or hendravirus). In some embodiments, the targeting moiety may be bound (fused or ligated) to the glycoprotein of a Rhabdoviridae virus such as bullous stomatitis New Jersey virus, bullous stomatitis Indiana virus, bullous stomatitis Aragoas virus, bullous stomatitis Maraba virus, bullous stomatitis Karajas virus, parainfluenza virus, Spodoptera frugiperda rhabdovirus isolate Sf G, Drosophila obscura Sigmavirus 10A, Wuhan insect virus 7, perch virus, or koi spring viremia virus. In some embodiments, the VSV protein is a mutant protein, e.g., as shown herein. In some embodiments, the targeting moiety is bound to the glycoprotein of a filoviridae virus such as Ebola virus, or to the glycoprotein of an arenaviridae virus such as Machupo virus.

[0308] In some embodiments, the target-directed moiety is scFv. In some embodiments, the target-directed moiety is a single-domain antibody. In some embodiments, the target-directed moiety is VHH.

[0309] In some embodiments, the target-directed moiety includes CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, or CXCR3, a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitor cells, a glycosylated CD43 epitope expressed on non-hematopoietic carcinomas, kinase anchor protein 4 (AKAP-4), and an adrenergic receptor. Autoantibodies against beta-3 (ADRB3), AFP, anaplastic lymphoma kinase (ALK), androgen receptor, angiopoietin-binding cell surface receptor 2 (Tie2), asialoglycoprotein receptor (ASGPR), desmoglein 1 (Dsgl), desmoglein 3 (Dsg3), B7H3 (CD276), biotin, bone marrow stromal cell antigen 2 (BST2), BST1 / CD157, cancer / testis antigen 1 (NY-ESO-1), cancer / testis antigen 2 (LAGE-la), carbonic anhydrase IX (CA1X), carcinoembryonic antigen (CEA), and CCCTC-binding factor (zinc finger protein)-like (BORIS or Brother) (of the Regulator of Chromosome X, chrompp65, C-MYC epitope tag, Cripto, CS1 (also known as CD2 subset 1, CRACC, SLAMF7, CD319, or 19A24), CSF2RA (GM-CSFR-alpha), C-type lectin domain family 12 member A (CLEC12A), C-type lectin-like molecule-1 (CLL-1 or CLECL1), cyclin Bl, cytochrome P450 IB 1 (CYP1B 1) DLL3, EBV-EBNA3c, EGF-bke module-containing mucin-like hormone receptor 2 (EMR2), elongation factor 2 mutant (ELF2M), ephrin B2, ephrin type A receptor 2 (EphA2), epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRviii), epidermal cell adhesion molecule (EPCAM), ERG, ETS translocation-variant gene 6 (ETV6-AML) located on chromosome 12p, IgA receptor Fc fragment (FCAR or CD89), Fc receptor-like 5 (FCRL5), fibroblast-activating protein alpha (FAP), FITC, Fms-like tyrosine kinase 3 (FLT3), folate receptor alpha (FRa or FR1), folate receptor beta (FRb), follicle-stimulating hormone receptor ( FSHR), Fos-related antigen 1, fucosyl-GMl, G protein-coupled receptor class C group 5 member D (GPRC5D), G protein-coupled receptor 20 (GPR20), GAD, ganglioside G2 (GD2), ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(ll)Cer), ganglioside GM3 (aNeu5Ac(2-3)bDClalp(l-4)bDGlcp(ll)Cer), GD3, GFR alpha 4, glycoprotein 100 (gplOO), glypican-3 (GPC3), gonadotropin hormone receptor (CGHR or GR), GpA33, GpNMB, GPRC5D, guanylyl cyclase C (GCC), heat shock protein 70-2 mutant (muthsp70-2), hepatitis A virus cell receptor 1 (HAVCR1), hexasaccharide portion of globoH glycoceramide (GloboH), high molecular weight melanoma-associated antigen (HMWMAA), HIV1 envelope glycoprotein, HLA, HLA-DOA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DM, HLA-DOB, HLA-DP, HLA-DQ, HLA-DR, HLA-G, HTLV1-Tax, human papillomavirus E6 (HPV E6), human papillomavirus E7 (HPV E7), human telomerase reverse transcriptase (hTERT), IgE, IL13Ra2, IL1 IRa, immunoglobulin lambda-like polypeptide 1 (IGLL1), influenza A hemagglutinin (HA), insulin-like growth factor 1 receptor (IGF-I receptor), interleukin-11 receptor alpha (IL-llRa), interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2), intestinal carboxylesterase, KIT (CD117), KSHV K8.1, KSHV-gH, LAMP1, Legmain, leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), luteinizing hormone receptor (LHR), Lewis (Y) antigen, Lewis Ag, Livl, Locus K9 (LY6K), low-conductance chloride channel, lymphocyte antigen 6 complex, lymphocyte antigen 75 (LY75), lymphocyte-specific protein tyrosine kinase (LCK), mammary gland differentiation antigen (NY-BR-1), melanoma antigen 1 recognized by T cells (MelanA or MARTI), melanoma-associated antigen 1 (MAGE-A1), melanoma carcinoma testis antigen-1 (MAD-CT-1), melanoma carcinoma testis antigen-2 (MAD-CT-2), apoptosis-induced melanoma inhibitor (ML-IAP), mesoserine, MPL, mucin 1 cell surface-related (MUC1), N-acetylglucosaminyl-transferase V (NA17), nectin-4, neuronal cell adhesion molecule (NCAM), NKG2D, NYBR1, Oncogene fusion protein (bcr-abl) consisting of O-acetyl-GD2 ganglioside (OAcGD2), olfactory receptor 51E2 (OR51E2), cleavage cluster region (BCR), and Abelson mouse leukemia virus oncogene homolog 1 (Abl), P53 variant, paired box protein Pax-3 (PAX3), paired box protein Pax-5 (PAX5), panexin 3 (PANX3), PDL1, P-glycoprotein, placenta-specific 1 (PLAC1), platelet-derived growth factor receptor beta (PDGFR-beta), polysialic acid, proacrosin-binding protein sp32 (OY-TES1), prostase, prostate cancer tumor antigen-1 (PCT Al or galectin 8), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), prostatic acid phosphatase (PAP), prostain, protease serine 21 (testicin or PRSS21), proteasome (prosomal macropain) subunit beta 9 (LMP2), PTK7, RasG12V, Ras homolog family member C (RhoC), rat sarcoma (Ras) mutant, advanced glycation end product receptor (RAGE-1), receptor tyrosine kinase-like orphan receptor 1 (ROR1), receptor tyrosine-protein kinase ERBB2 or Her-22 / neu, renal ubiquitous receptor 1 (RU1), renal ubiquitous receptor 2 (RU2), sarcoma translocation breakpoint, serine 2 (TMPRSS2) ETS fusion gene, sialyl Lewis adhesion molecule (sLe), SLAMF4, SLAMF6, Slea (CA19.9 or sialyl Lewis antigen), sperm Sub-protein 17 (SPA17), squamous cell carcinoma antigen 3 recognized by T cells (SART3), stage-specific embryonic antigen-4 (SSEA-4), STEAP1, Survivin, synovial sarcoma X-section 2 (SSX2), TCR gamma surrogate leading frame protein (TARP), TCR-beta 1 chain, TCR-beta 2 chain, TCR-delta chain, TCR gamma chain, TCR gamma-delta, telomerase, TGF-beta R2, antigen recognized by TNT antibody, thyroid-stimulating hormone receptor (TSHR), Timl- / HVCR1, tissue factor 1 (TF1), Tn It binds to ag, Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)), TNF receptor family member B cell maturation (BCMA), transglutaminase 5 (TGS5), transmembrane protease, TROP2, tumor endothelial marker 1 (TEM1 / CD248), tumor endothelial marker 7-related (TEM7R), tumor protein p53 (p53), tumor-associated glycoprotein 72 (TAG72), tyrosinase, tyrosinase-related protein 2 (TRP-2), uroplakin 2 (UPK2), vascular endothelial growth factor receptor 2 (VEGFR2), V-myc avian myeloidosis virus oncogene neuroblastoma-derived homolog (MYCN), Wilms tumor protein (WT1), or X antigen family member 1A (XAGE1). In some embodiments, the target-directed moiety binds to CD7. In some embodiments, the target-directed moiety binds to CD8.

[0310] In some embodiments, the target-directing portion binds to a target present on a cell, such as an immune cell. In some embodiments, the cell is an immune cell. Such immune cells include, but are not limited to, T cells, B cells, NK cells, dendritic cells, neutrophils, macrophages, cancer cells, or, for example, CD3+ T cells, CD4+ T cells, CD7+ T cells, CD8+ T cells, CD19+ B cells, CD19+ cancer cells, CD20+ B cells, CD20+ cancer cells, CD30+ lung epithelial cells, CD34+ hematopoietic stem cells, CD105+ endothelial cells, CD105+ hematopoietic stem cells, CD117+ hematopoietic stem cells, CD133+ cancer cells, EpCAM+ cancer cells, GluA2+ neurons, GluA4+ neurons, hematopoietic stem cells, hepatocytes, Her2 / Neu+ cancer cells, NKG2D+ natural killer cells, SLC1A3+ astrocytes, SLC7A10+ adipocytes, etc. In some embodiments, the cell is a T cell. In some embodiments, the cells are B cells. In some embodiments, the cells are CD7+ T cells and / or CD8+ T cells.

[0311] In some embodiments, the target-directed portion (polypeptide) can be bound to CD7.

[0312] In some embodiments, the polypeptide binds to CD7. In some embodiments, the polypeptide that binds to CD7 is an antibody that binds to non-human primate CD7. In some embodiments, the polypeptide that binds to CD7 is an antibody that binds to human CD7. The sequence of human CD7 (UniProtKB P09564) is as follows (SEQ ID NO: 29): MAGPPRLLLLPLLLALARGLPGALAAQEVQQSPHCTTVPVGASVNITCSTSGGLRGIYLRQLGPQPQDIIYYEDGVVPTTDRRFRGRIDFSGSQDNLTITMHRLQLSDTGTYTCQAITEVNVYGSGTLVLVTEEQSQGWHRCSDAPPRASALPAPPTGSALPDPQTASALPDPPAASALPAALAVISFLLGLGLGVACVLARTQIKKLCSWRDKNSAACVVYEDMSHSRCNTLSSPNQYQ(Sequence ID 29)

[0313] In some embodiments, the CD7 antibody includes an Fc region. The Fc region can be conjugated to the heavy or light chain of the antibody. The Fc region may be directly fused to the heavy or light chain of the antibody, or indirectly fused to the heavy or light chain of the antibody via, for example, a peptide linker provided herein. In some embodiments, the Fc region is IgG Fc. In some embodiments, IgG is selected from IgG1, IgG2, IgG3, or IgG4. In some embodiments, IgG fc is IgG1 Fc. In some embodiments, the antibody includes the Fc constant region of SEQ ID NO: 26 described below: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(Sequence ID 26)

[0314] In some embodiments, IgG fc is IgG2 Fc. In some embodiments, the antibody includes the Fc constant region of SEQ ID NO: 27 described below: STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (Sequence ID 27)

[0315] In some embodiments, IgG fc is IgG4 Fc. In some embodiments, the antibody includes the Fc constant region of SEQ ID NO: 28 described below: STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (Sequence ID 28)

[0316] In some embodiments, IgG Fc is a variant of the IgG1 Fc protein (SEQ ID NO: 26). In some embodiments, the variant IgG1 Fc protein contains one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO: 26. Any of the mutations L234A, L235A, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO: 26 may or may not be present, and these mutations may be combined in any combination. In some embodiments, the variant IgG1 Fc protein contains mutations corresponding to L234A and L235A of SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein contains a mutation corresponding to N297A of SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein contains a mutation corresponding to P329G in SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein contains mutations corresponding to L234A, L235A, N297A, and P329G in SEQ ID NO: 83. In some embodiments, the variant IgG1 Fc protein contains a mutation corresponding to I253A in SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein contains a mutation corresponding to H310A in SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein contains a mutation corresponding to H435A in SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein contains mutations corresponding to I253A, H310A, and H435A in SEQ ID NO: 26.

[0317] In some embodiments, IgG Fc is a variant of the IgG2 Fc protein (SEQ ID NO: 27). In some embodiments, the variant IgG2 Fc protein contains one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A at the position corresponding to SEQ ID NO: 27. Any of N297A, P329G, I253A, H310A, and H435A in SEQ ID NO: 27 may or may not be present, and these mutations may be combined in any combination. In some embodiments, the variant IgG2 Fc protein contains the mutation corresponding to N297A in SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein contains the mutation corresponding to P329G in SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein contains the mutations corresponding to N297A and P329G in SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein contains the mutation corresponding to I253A in SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein contains a mutation corresponding to H310A in SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein contains a mutation corresponding to H435A in SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein contains mutations corresponding to I253A, H310A, and H435A in SEQ ID NO: 27.

[0318] In some embodiments, the IgG Fc protein is a variant of the IgG4 Fc protein (SEQ ID NO: 28). In some embodiments, the variant IgG4 Fc protein contains one or more mutations selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A, and H435A at the position corresponding to SEQ ID NO: 28. Any of the mutations S228P, L235E, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO: 28 may or may not be present, and these mutations may be combined in any combination. In some embodiments, the variant IgG4 Fc protein contains the mutation corresponding to S228P of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein contains the mutation corresponding to L235E of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein contains the mutation corresponding to N297A of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein contains a mutation corresponding to P329G in SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein contains mutations corresponding to S228P, L235E, N297A, and P329G in SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein contains a mutation corresponding to I253A in SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein contains a mutation corresponding to H310A in SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein contains a mutation corresponding to H435A in SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein contains mutations corresponding to I253A, H310A, and H435A in SEQ ID NO: 28.

[0319] In some embodiments, the Fc region comprises a variant Fc polypeptide. In some embodiments, the variant Fc polypeptide is a variant Fc polypeptide provided in PCT Publication WO2024026284 (which is incorporated herein by reference in its entirety). In some embodiments, the variant Fc polypeptide comprises an amino acid sequence that is at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 82. EPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMASRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLAQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNAYTQKSLSLSPGK(Sequence ID 82)

[0320] In some embodiments, the variant Fc polypeptide contains the amino acid sequence of SEQ ID NO: 82.

[0321] In some embodiments, the target-directing portion is coupled to the CD7 and includes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3, VH, and VL as shown in Tables 1 and 2 below. [Table 1] [Table 2]

[0322] The VH and VL sequences may be any structure including, but not limited to, an scFv structure in which the VH and VL regions are linked by a peptide linker. An example of a peptide linker that can be used to link the various peptides provided herein is (GGGGS) nExamples include, but are not limited to, (SEQ ID NO: 64) (where n is independently 1 to 4). In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, the variable region is not linked by a peptide linker. In some embodiments, the polypeptide includes SEQ ID NOs: 42 and 43. In some embodiments, the target-directed portion is of formula V L -ZV H The linked peptide is represented by (wherein Z is a peptide linker). In some embodiments, the target-directed portion includes a heavy chain variable region shown in SEQ ID NO: 42, linked to a light chain variable region shown in SEQ ID NO: 43 via the linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72). In some embodiments, the peptide linker is linked to V H V connected to L The target-directed portion, including the element, has the following arrangement. DILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSS(Sequence ID 44)

[0323] In some embodiments, the target-directing portion is given by equation V H -ZV L The linked peptide is represented by (wherein Z is a peptide linker). In some embodiments, the target-directed portion includes a heavy chain variable region shown in SEQ ID NO: 42, linked to a light chain variable region shown in SEQ ID NO: 43 via the linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72). In some embodiments, the peptide linker is linked to V LV connected to H The target-directed portion, including the element, has the following arrangement. QVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGGGSDILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKR (Sequence ID 45)

[0324] In some embodiments, the target-directed portion (polypeptide) can be bound to CD8.

[0325] In some embodiments, the polypeptide binds to CD8. In some embodiments, the polypeptide binds to CD8 alpha. In some embodiments, the polypeptide binds to CD8 beta. In some embodiments, the polypeptide binds to a CD8 heterodimer. In some embodiments, the CD8 heterodimer includes a CD8 alpha subunit and a CD8 beta subunit. In some embodiments, the polypeptide binds to a CD8 alpha homodimer. In some embodiments, the polypeptide that binds to CD8 is an antibody that binds to non-human primate CD8. In some embodiments, the antibody that binds to non-human primate CD8 is an antibody that binds to non-human primate CD8 alpha. In some embodiments, the antibody that binds to non-human primate CD8 is an antibody that binds to non-human primate CD8 beta. In some embodiments, the antibody that binds to non-human primate CD8 is an antibody that binds to a non-human primate CD8 alpha homodimer. In some embodiments, the antibody that binds to non-human primate CD8 is an antibody that binds to a non-human primate CD8 heterodimer. In some embodiments, the polypeptide that binds to CD8 is an antibody that binds to human CD8. In some embodiments, the antibody that binds to human CD8 is an antibody that binds to human CD8 alpha. In some embodiments, the antibody that binds to human CD8 is an antibody that binds to human CD8 beta. In some embodiments, the antibody that binds to human CD8 is an antibody that binds to human CD8 alpha homodimer. In some embodiments, the antibody that binds to human CD8 is an antibody that binds to human CD8 heterodimer. The sequence of human CD8 alpha (UniProtKB Q8TAW8) is as follows (SEQ ID NO: 46): MALPVTALLLPLALLLHAARPSQFRVSPLDRTWNLGETVELKCQVLLSNPTSGCSWLFQPRGAAASPTFLLYLSQNKPKAAEGLDTQRFSGKRLGDTFVLTLSDFRRENEGCYFCSALSNSIMYFSHFVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHRNRRRVCKCPRPVVKSGDKPSLSARYV(Sequence ID 46)

[0326] The sequence of human CD8 beta (UniProtKB Q8TD28) is as follows (sequence number 47): MRPRLWLLLAAQLTVLHGNSVLQQTPAYIKVQTNKMVMLSCEAKISLSNMRIYWLRQRQAPSSDSHHEFLALWDSAKGTIHGEEVEQEKIAVFRDASRFILNLTSVKPEDSGIYFCMIVGSPELTFGKGTQLSVVDFLPTTAQPTKKSTLKKRVCRLPRPETQKGPLCSPITLGLLVAGVLVLLVSLGVAIHLCCRRRRARLRFMKQLYK (Sequence ID 47)

[0327] In some embodiments, the CD8 antibody includes an Fc region. The Fc region can be conjugated to the heavy or light chain of the antibody. The Fc region may be directly fused to the heavy or light chain of the antibody, or indirectly fused to the heavy or light chain of the antibody via, for example, a peptide linker provided herein. In some embodiments, the Fc region is IgG Fc provided herein. In some embodiments, IgG is selected from IgG1, IgG2, IgG3, or IgG4. In some embodiments, IgG fc is IgG1 Fc provided herein. In some embodiments, the antibody includes the Fc constant region of SEQ ID NO: 26. In some embodiments, IgG fc is IgG2 Fc provided herein. In some embodiments, the antibody includes the Fc constant region of SEQ ID NO: 27. In some embodiments, IgG fc is IgG4 Fc provided herein. In some embodiments, the antibody includes the Fc constant region of SEQ ID NO: 28.

[0328] In some embodiments, the target-directing portion is coupled to the CD8 and includes HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3, VH, and VL as shown in Tables 3 and 4 below. [Table 3] [Table 4]

[0329] The VH and VL sequences may be any structure including, but not limited to, an scFv structure in which the VH and VL regions are linked by a peptide linker. An example of a peptide linker that can be used to link the various peptides provided herein is (GGGGS) nExamples include, but are not limited to, (SEQ ID NO: 64) (where n is independently 1 to 4). In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, the variable region is not linked by a peptide linker. In some embodiments, the polypeptide includes SEQ ID NOs: 60 and 61.

[0330] In some embodiments, the target-directing portion is given by equation V L -ZV H The peptide comprises a linked peptide represented by (wherein Z is a peptide linker). In some embodiments, the target-directed portion comprises a heavy chain variable region shown in SEQ ID NO: 60 linked to a light chain variable region shown in SEQ ID NO: 61 via the linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72). In some embodiments, via the peptide linker V H V connected to L The target-directed portion, including the element, has the following arrangement. NIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSEVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSS(Sequence ID 62)

[0331] In some embodiments, the target-directing portion is given by equation V H -ZV LThe peptide comprises a linked peptide represented by (wherein Z is a peptide linker). In some embodiments, the target-directed portion comprises a heavy chain variable region shown in SEQ ID NO: 60 linked to a light chain variable region shown in SEQ ID NO: 61 via the linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72). In some embodiments, via the peptide linker V L V connected to H The target-directed portion, including the element, has the following arrangement. EVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSNIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKR (Sequence ID 63)

[0332] In some embodiments, the target-directed moiety includes an amino acid sequence having at least 70% identity with SEQ ID NO: 44, or is substantially similar to SEQ ID NO: 44, or is an active fragment of SEQ ID NO: 44. In some embodiments, the target-directed moiety includes an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with SEQ ID NO: 44. In some embodiments, the target-directed moiety includes the amino acid sequence of SEQ ID NO: 44.

[0333] In some embodiments, the target-directed moiety includes an amino acid sequence having at least 70% identity with SEQ ID NO: 45, or is substantially similar to SEQ ID NO: 45, or is an active fragment of SEQ ID NO: 45. In some embodiments, the target-directed moiety includes an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with SEQ ID NO: 45. In some embodiments, the target-directed moiety includes the amino acid sequence of SEQ ID NO: 45.

[0334] In some embodiments, the target-directed moiety comprises an amino acid sequence having at least 70% identity with SEQ ID NO: 62, or is substantially similar to SEQ ID NO: 62, or is an active fragment of SEQ ID NO: 62. In some embodiments, the target-directed moiety comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with SEQ ID NO: 62. In some embodiments, the target-directed moiety comprises the amino acid sequence of SEQ ID NO: 62.

[0335] In some embodiments, the target-directed moiety comprises an amino acid sequence having at least 70% identity with SEQ ID NO: 63, or is substantially similar to SEQ ID NO: 63, or is an active fragment of SEQ ID NO: 63. In some embodiments, the target-directed moiety comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with SEQ ID NO: 63. In some embodiments, the target-directed moiety comprises the amino acid sequence of SEQ ID NO: 63.

[0336] In some embodiments, the target-directed moiety provided herein is bound to the surface of the virus via a stalk portion S1. In some embodiments, the target-directed moiety is represented by the formula T-S1, where T is the target-directed moiety provided herein and S1 is the stalk portion. In some embodiments, the stalk portion S1 is as provided in PCT Publication WO2024026284 (which is incorporated herein by reference in its entirety). In some embodiments, the stalk portion S1 comprises a variant Fc protein provided herein, represented by the formula L1-Fc-L2-X1, where L1 is a linker or is absent, Fc is a variant Fc protein, L2 is a linker or is absent, and X1 is a polypeptide containing a transmembrane domain. Thus, in some embodiments, the formula representing the target-directed moiety can also be written as T-L1-Fc-L2-X1. In some embodiments, the stalk protein S1 does not contain variant Fc region variants and is represented by the formula L3-X1, where L3 is a mobile peptide linker and X1 is a polypeptide containing a transmembrane domain. Thus, in some embodiments, the formula representing the target-directing moiety can also be written as T-L3-X1. In some embodiments, the polypeptide containing the transmembrane domain X1 is represented by the formula ECD-T M-Contains the polypeptide of ICD, where ECD is either the extracellular domain of a cell surface protein or a fragment thereof, or is absent, T M T is the transmembrane domain of a transmembrane protein, and ICD is either a protein that facilitates the incorporation of the target-directing portion into the intracellular domain of a protein or the envelope of a viral particle, or it is absent. Therefore, the formula representing the target-directing portion linked to the stalk is T-L1-Fc-L2-ECD-T M -ICD or T-L3-ECD-T M -ICD can also be written as -ICD. L1, L2, L3, Fc, ECD, T M Exemplary identities of the ICD can be found in PCT Publication WO2024026284 (which is incorporated herein by reference in its entirety).

[0337] In some embodiments, the target-directing portion is T-L1-Fc-L2-ECD-T M -Has the formula ICD. In some embodiments, T includes an amino acid sequence having at least 90% identity with SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 62, or SEQ ID NO: 63. In some embodiments, L1 is present and includes the amino acid sequence of SEQ ID NO: 72. In some embodiments, Fc includes an amino acid sequence having at least 90% identity with SEQ ID NO: 82. In some embodiments, L2 is absent. In some embodiments, ECD includes an amino acid sequence having at least 90% identity with SEQ ID NO: 83. KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP(Sequence ID 83) In some embodiments, T M It contains an amino acid sequence that has at least 90% identity with SEQ ID NO: 84. FWVLVVVGGVLACYSLLVTVAFIIFWV (Sequence ID 84) In some embodiments, the ICD includes an amino acid sequence containing an env embedded motif, the env embedded motif containing the amino acid sequence of SEQ ID NO: 85. NRVRQGYS (Sequence ID 85)

[0338] In some embodiments, the target-directing portion is T-L1-Fc-L2-ECD-T M -Has the formula ICD. In some embodiments, T includes the amino acid sequence of SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 62, or SEQ ID NO: 63. In some embodiments, L1 is present and includes the amino acid sequence of SEQ ID NO: 72. In some embodiments, Fc includes the amino acid sequence of SEQ ID NO: 82. In some embodiments, L2 is absent. In some embodiments, ECD includes the amino acid sequence of SEQ ID NO: 83. In some embodiments, T M This includes the amino acid sequence of SEQ ID NO: 84. In some embodiments, the ICD includes an amino acid sequence containing an env embedded motif, the env embedded motif containing the amino acid sequence of SEQ ID NO: 85.

[0339] In some embodiments, the target-directing portion is T-L1-Fc-L2-ECD-T M -Has the formula ICD. In some embodiments, T includes the amino acid sequence of SEQ ID NO: 44 or SEQ ID NO: 45. In some embodiments, L1 is present and includes the amino acid sequence of SEQ ID NO: 72. In some embodiments, Fc includes the amino acid sequence of SEQ ID NO: 82. In some embodiments, L2 is absent. In some embodiments, ECD includes the amino acid sequence of SEQ ID NO: 83. In some embodiments, T M This includes the amino acid sequence of SEQ ID NO: 84. In some embodiments, the ICD includes an amino acid sequence containing an env embedded motif, the env embedded motif containing the amino acid sequence of SEQ ID NO: 85.

[0340] In some embodiments, the target-directing portion is T-L1-Fc-L2-ECD-T M-Has the formula ICD. In some embodiments, T contains the amino acid sequence of SEQ ID NO: 45. In some embodiments, L1 is present and contains the amino acid sequence of SEQ ID NO: 72. In some embodiments, Fc contains the amino acid sequence of SEQ ID NO: 82. In some embodiments, L2 is absent. In some embodiments, ECD contains the amino acid sequence of SEQ ID NO: 83. In some embodiments, T M This includes the amino acid sequence of SEQ ID NO: 84. In some embodiments, the ICD includes an amino acid sequence containing an env embedded motif, the env embedded motif containing the amino acid sequence of SEQ ID NO: 85.

[0341] In some embodiments, the target-directing portion is T-L3-ECD-T M -The formula is ICD. In some embodiments, T includes an amino acid sequence having at least 90% identity with SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 62, or SEQ ID NO: 63. In some embodiments, L3 includes the amino acid sequence of SEQ ID NO: 64, and n is 1, 2, or 4. In some embodiments, ECD includes an amino acid sequence having at least 90% identity with SEQ ID NO: 86. FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (Sequence ID 86) In some embodiments, T M It contains an amino acid sequence that has at least 90% identity with SEQ ID NO: 87. IYIWAPLAGTCGVLLLSLVITLYCNHRN (Sequence ID 87) In some embodiments, the ICD includes an amino acid sequence containing an env embedded motif, the env embedded motif containing the amino acid sequence of SEQ ID NO: 85 or SEQ ID NO: 88. GGTETSQVAPA (Sequence ID 88)

[0342] In some embodiments, the target-directing portion is T-L3-ECD-T M-Has the formula ICD. In some embodiments, T includes the amino acid sequence of SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 62, or SEQ ID NO: 63. In some embodiments, L3 includes the amino acid sequence of SEQ ID NO: 64, and n is 1, 2, or 4. In some embodiments, ECD includes the amino acid sequence of SEQ ID NO: 86. In some embodiments, T M This includes the amino acid sequence of SEQ ID NO: 87. In some embodiments, the ICD includes an amino acid sequence containing an env embedded motif, the env embedded motif containing the amino acid sequence of SEQ ID NO: 85 or SEQ ID NO: 88.

[0343] In some embodiments, the target-directing portion is T-L3-ECD-T M -Has the formula ICD. In some embodiments, T includes the amino acid sequence of SEQ ID NO: 44 or SEQ ID NO: 45. In some embodiments, L3 includes the amino acid sequence of SEQ ID NO: 64, where n is 1, 2, or 4. In some embodiments, ECD includes the amino acid sequence of SEQ ID NO: 86. In some embodiments, T M This includes the amino acid sequence of SEQ ID NO: 87. In some embodiments, the ICD includes an amino acid sequence containing an env embedded motif, the env embedded motif containing the amino acid sequence of SEQ ID NO: 85 or SEQ ID NO: 88.

[0344] In some embodiments, the target-directing portion is T-L3-ECD-T M -Has the formula ICD. In some embodiments, T comprises the amino acid sequence of SEQ ID NO: 45. In some embodiments, L3 comprises the amino acid sequence of SEQ ID NO: 64, where n is 1, 2, or 4. In some embodiments, ECD comprises the amino acid sequence of SEQ ID NO: 86. In some embodiments, T M This includes the amino acid sequence of SEQ ID NO: 87. In some embodiments, the ICD includes an amino acid sequence containing an env embedded motif, the env embedded motif containing the amino acid sequence of SEQ ID NO: 85 or SEQ ID NO: 88.

[0345] In some embodiments, the target-directed portion containing the formula T-S1 includes an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with respect to SEQ ID NO: 89. (Sequence ID 89) In some embodiments, the target-directed portion containing the formula T-S1 includes an amino acid sequence having 90% identity with SEQ ID NO: 89. In some embodiments, the target-directed portion containing the formula T-S1 includes an amino acid sequence having 95% identity with SEQ ID NO: 89. In some embodiments, the target-directed portion containing the formula T-S1 includes an amino acid sequence having 98% identity with SEQ ID NO: 89. In some embodiments, the target-directed portion containing the formula T-S1 includes the amino acid sequence of SEQ ID NO: 89.

[0346] In some embodiments, a viral vector comprising a variant VSV-G protein provided herein, and comprising a target-directed moiety provided herein, further comprises a nucleic acid molecule encoding a heterogeneous molecule of interest or “cargo.” For example, “heterogeneous molecule of interest” is intended to refer to any product that can be encoded by the nucleic acid molecule. In non-limiting examples, “cargo” or “heterogeneous molecule of interest” may refer to siRNA, shRNA, peptides, polypeptides, proteins, viral payloads, viral genomes, or combinations thereof. In some embodiments, the polypeptide is a chimeric antigen receptor (“CAR”).

[0347] As used herein, “chimeric antigen receptor” or “CAR” refers to an antigen-binding domain that is directly or indirectly fused (e.g., via a hinge or transmembrane domain) to an intracellular signaling domain that can activate or stimulate immune cells. Most commonly, the extracellular binding domain of a CAR consists of a single-chain variable fragment (scFv) obtained by fusing the variable heavy chain region and variable light chain region of a mouse monoclonal antibody or a humanized monoclonal antibody. Alternatively, scFv obtained from Fab (not from an antibody, but e.g., from a Fab library) can be used. In various embodiments, this scFv is fused to a transmembrane domain, and then to an intracellular signaling domain. However, the antigen-binding domain can be any molecule that can bind to a target on a cell. For example, the antigen-binding domain of a CAR can be an antibody, an scFv antibody, an antigen-binding domain, ankyrin repeat (e.g., DARPIN), a VHH domain antibody, The CAR may be a nanobody, a single-domain antibody, an FN3 domain, or any combination thereof. In some embodiments, the CAR includes those that yield only a CD3ζ signal upon antigen binding. In some embodiments, the CAR includes those that provide both co-stimulation (e.g., CD28 or CD137) and activation (CD3ζ). In some embodiments, the CAR includes those that provide multiple co-stimulations (e.g., CD28 and CD137) and activation (CD3ζ). In various embodiments, the CAR is selected to have high affinity or avidity to the antigen. In some embodiments, the CAR also includes a 4-1BB domain. These are merely illustrative and not limiting to these embodiments, and any chimeric antigen receptor can be delivered together with the viral particles and vectors shown herein. These are non-limiting examples of CARs, and any CAR construct can be encoded by a nucleic acid molecule.

[0348] In some embodiments, the antigen-binding domain of CAR is V H Domain or V L Includes domain or V H Domain and VL Includes domains. In some embodiments, V H The domain includes an amino acid sequence, or any value or range between them, that has at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with sequence number 73. EVQLVESGGGLVQPGRSLRLSCAASGFTFNDYAMHWVRQAPGKGLEWVSTISWNSGSIGYADSVKGRFTISRDNAKKSLYLQMNSLRAEDTALYYCAKDIQYGNYYYGMDVWGQGTTVTVSS(Sequence ID 73) In some embodiments, V H The domain contains an amino acid sequence having at least 90% identity with SEQ ID NO: 73. In some embodiments, V H The domain contains an amino acid sequence having at least 95% identity with SEQ ID NO: 73. In some embodiments, V H The domain contains an amino acid sequence having at least 98% identity with SEQ ID NO: 73. In some embodiments, V H The domain contains an amino acid sequence that has at least 99% identity with SEQ ID NO: 73. In some embodiments, V H The domain contains an amino acid sequence having the sequence of sequence number 73.

[0349] In some embodiments, V L The domain contains an amino acid sequence having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with respect to sequence number 74, or any value or range in between. EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPITFGQGTRLEIK (Sequence ID 74) In some embodiments, V L The domain contains an amino acid sequence having at least 90% identity with SEQ ID NO: 74. In some embodiments, V L The domain contains an amino acid sequence having at least 95% identity with SEQ ID NO: 74. In some embodiments, V L The domain contains an amino acid sequence having at least 98% identity with SEQ ID NO: 74. In some embodiments, V L The domain contains an amino acid sequence that has at least 99% identity with SEQ ID NO: 74. In some embodiments, V L The domain contains an amino acid sequence having the sequence of sequence number 74.

[0350] In some embodiments, the antigen-binding domain of CAR is V H Domain and V L Includes domain. In some embodiments, V H Domain and V L The domain is not linked by a linker peptide. In some embodiments, V H and V L The domains are linked by linker peptides such as those provided herein, (GGGGS) n (Sequence ID 64) (where each n is independently 1 to 5) includes, but is not limited to, n = 1 in some embodiments. In some embodiments, n = 2 in some embodiments. In some embodiments, n = 3 in some embodiments. In some embodiments, n = 4 in some embodiments. In some embodiments, n = 5 in some embodiments.

[0351] In some embodiments, V H Domain and V L The antigen-binding domain of the CAR containing the domain has at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with SEQ ID NO: 73. HV containing a domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with sequence number 74. L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR containing the domain has at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with SEQ ID NO: 73. H V, which includes the domain and has at least 90% identity with SEQ ID NO: 74 L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR containing the domain has at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with SEQ ID NO: 73. H V, which includes the domain and has at least 95% identity with SEQ ID NO: 74 L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR containing the domain has at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with SEQ ID NO: 73. H V, which includes the domain and has at least 98% identity with sequence number 74 L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR containing the domain has at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with SEQ ID NO: 73. HV, which includes the domain and has at least 99% identity with SEQ ID NO: 74 L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR containing the domain has at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with SEQ ID NO: 73. H V containing a domain and having the sequence of sequence number 74 L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR, including the domain, has at least 90% identity with SEQ ID NO: 73. H V containing a domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with sequence number 74. L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR, including the domain, has at least 95% identity with SEQ ID NO: 73. H V containing a domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with sequence number 74. L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR, including the domain, has at least 98% identity with SEQ ID NO: 73. H V containing a domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with sequence number 74. L Includes. In some embodiments, V H Domain and VL The antigen-binding domain of the CAR, including the domain, has at least 99% identity with SEQ ID NO: 73. H V containing a domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with sequence number 74. L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR, which includes the domain, has the amino acid sequence of SEQ ID NO: 73. H V containing a domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with sequence number 74. L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR, including the domain, has at least 90% identity with SEQ ID NO: 73. H V, which includes the domain and has at least 90% identity with SEQ ID NO: 74 L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR, including the domain, has at least 95% identity with SEQ ID NO: 73. H V, which includes the domain and has at least 90% identity with SEQ ID NO: 74 L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR, including the domain, has at least 90% identity with SEQ ID NO: 73. H V, which includes the domain and has at least 95% identity with SEQ ID NO: 74 L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR, including the domain, has at least 95% identity with SEQ ID NO: 73. HV, which includes the domain and has at least 95% identity with SEQ ID NO: 74 L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR, including the domain, has at least 98% identity with SEQ ID NO: 73. H V, which includes the domain and has at least 98% identity with sequence number 74 L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR, including the domain, has at least 99% identity with SEQ ID NO: 73. H V, which includes the domain and has at least 99% identity with SEQ ID NO: 74 L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR, which includes the domain, has the amino acid sequence of SEQ ID NO: 73. H V containing a domain and having the amino acid sequence of SEQ ID NO: 74 L Includes.

[0352] In some embodiments, the antigen-binding domain of CAR is V H -ZV L The formula includes the expression, and in the formula, V H Z is a heavy chain variable region containing the amino acid sequence of SEQ ID NO: 73, Z is a linker containing the amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO: 77), and V L This is a light chain variable region containing the amino acid sequence of SEQ ID NO: 74. In some embodiments, V H -ZV L The antigen-binding domain of a CAR having the formula shown has the following amino acid sequence. EVQLVESGGGLVQPGRSLRLSCAASGFTFNDYAMHWVRQAPGKGLEWVSTISWNSGSIGYADSVKGRFTISRDNAKKSLYLQMNSLRAEDTALYYCAKDIQYGNYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPITFGQGTRLEIK(Sequence ID 75) In some embodiments, the antigen-binding domain of CAR includes an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the sequence of SEQ ID NO: 75. In some embodiments, the antigen-binding domain of CAR includes an amino acid sequence having at least 90% identity with the sequence of SEQ ID NO: 75. In some embodiments, the antigen-binding domain of CAR includes an amino acid sequence having at least 95% identity with the sequence of SEQ ID NO: 75. In some embodiments, the antigen-binding domain of CAR includes an amino acid sequence having at least 98% identity with the sequence of SEQ ID NO: 75. In some embodiments, the antigen-binding domain of CAR includes an amino acid sequence having at least 99% identity with the sequence of SEQ ID NO: 75. In some embodiments, the antigen-binding domain of CAR includes the amino acid sequence of SEQ ID NO: 75.

[0353] In some embodiments, the antigen-binding domain of CAR is V L -ZV H The formula includes the expression, and in the formula, V L Z is a light chain variable region containing the amino acid sequence of SEQ ID NO: 74, Z is a linker containing the amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO: 77), and V H This is a light chain variable region containing the amino acid sequence of SEQ ID NO: 73. In some embodiments, V L -ZV HThe antigen-binding domain of a CAR having the formula shown has the following amino acid sequence. EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPITFGQGTRLEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGRSLRLSCAASGFTFNDYAMHWVRQAPGKGLEWVSTISWNSGSIGYADSVKGRFTISRDNAKKSLYLQMNSLRAEDTALYYCAKDIQYGNYYYGMDVWGQGTTVTVSS(Sequence ID 76) In some embodiments, the antigen-binding domain of CAR includes an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the sequence of SEQ ID NO: 76. In some embodiments, the antigen-binding domain of CAR includes an amino acid sequence having at least 90% identity with the sequence of SEQ ID NO: 76. In some embodiments, the antigen-binding domain of CAR includes an amino acid sequence having at least 95% identity with the sequence of SEQ ID NO: 76. In some embodiments, the antigen-binding domain of CAR includes an amino acid sequence having at least 98% identity with the sequence of SEQ ID NO: 76. In some embodiments, the antigen-binding domain of CAR includes an amino acid sequence having at least 99% identity with the sequence of SEQ ID NO: 76. In some embodiments, the antigen-binding domain of CAR includes the amino acid sequence of SEQ ID NO: 76.

[0354] In some embodiments, the antigen-binding domain of CAR is V H Domain or V L Includes domain or V H Domain and V L Includes domains. In some embodiments, V HThe domain includes an amino acid sequence, or any value or range, that has at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with sequence number 78. DIVLTQSPAILSASPGEKVTMTCRASSSVNYMDWYQKKPGSSPKPWIYATSNLASGVPARFSGSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGGGTKLEIKGSTS (Sequence ID 78) In some embodiments, V H The domain contains an amino acid sequence having at least 90% identity with SEQ ID NO: 78. In some embodiments, V H The domain contains an amino acid sequence having at least 95% identity with SEQ ID NO: 78. In some embodiments, V H The domain contains an amino acid sequence having at least 98% identity with SEQ ID NO: 78. In some embodiments, V H The domain contains an amino acid sequence that has at least 99% identity with SEQ ID NO: 78. In some embodiments, V H The domain contains an amino acid sequence having the sequence of sequence number 78.

[0355] In some embodiments, V L The domain includes an amino acid sequence, or any value or range, that has at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with sequence number 79. EVQLQQSGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSADYYCARSNYYGSSYWFFDVWGAGTTVTVSS(Sequence ID 79) In some embodiments, V LThe domain contains an amino acid sequence having at least 90% identity with SEQ ID NO: 79. In some embodiments, V L The domain contains an amino acid sequence having at least 95% identity with SEQ ID NO: 79. In some embodiments, V L The domain contains an amino acid sequence having at least 98% identity with SEQ ID NO: 79. In some embodiments, V L The domain contains an amino acid sequence that has at least 99% identity with SEQ ID NO: 79. In some embodiments, V L The domain contains an amino acid sequence having the sequence of sequence number 79.

[0356] In some embodiments, V H Domain and V L The antigen-binding domain of the CAR containing the domain has at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with SEQ ID NO: 78. H V containing a domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with sequence number 79 L Includes. In some embodiments, V H Domain and V L The antigen-binding domain of the CAR containing the domain has at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%,...

Claims

1. A pharmaceutical composition, (i) Lentiviral vectors and (ii) A pharmaceutically acceptable buffer solution with a concentration of approximately 5 mM to approximately 100 mM, (iii) Pharmaceutically acceptable salts with concentrations of approximately 100 mM to approximately 800 mM, (iv) Approximately 1% (w / v) to approximately 5% (w / v) of sugar, (v) Contains a protein excipient in an amount of approximately 0.1% (w / v) to approximately 3% (w / v), The pharmaceutical composition having a pH of about 6.0 to about 8.

0.

2. The aforementioned lentiviral vector is approximately 1.0E ＋０５ ~Approximately 1.0E ＋０９ The pharmaceutical composition according to claim 1, present at a concentration of TU / mL.

3. The pharmaceutical composition according to claim 1 or 2, wherein the pharmaceutically acceptable buffer is histidine buffer, HEPES, phosphate buffer, citrate buffer, acetate buffer, succinate buffer, phosphate buffer, acetate buffer, citrate buffer, succinate buffer, ascorbic acid buffer, glutamate buffer, lactate buffer, maleate buffer, trometamol buffer, or gluconate buffer, or any combination thereof.

4. The pharmaceutical composition according to any one of claims 1 to 3, wherein the pharmaceutically acceptable buffer is a histidine buffer.

5. The pharmaceutical composition according to claim 4, wherein the histidine buffer is present at a concentration of about 10 mM to about 30 mM.

6. The pharmaceutical composition according to any one of claims 1 to 5, wherein the pharmaceutical composition has a pH of about 6.5 to about 7.

5.

7. The pharmaceutical composition according to any one of claims 1 to 6, wherein the pharmaceutically acceptable salt is sodium chloride, potassium chloride, magnesium chloride, or calcium chloride, or any combination thereof.

8. The pharmaceutical composition according to any one of claims 1 to 7, wherein the pharmaceutically acceptable salt is sodium chloride.

9. The pharmaceutical composition according to claim 8, wherein the sodium chloride is present at a concentration of about 100 mM to about 250 mM.

10. The pharmaceutical composition according to any one of claims 1 to 9, wherein the sugar is sucrose, trehalose, or a combination thereof.

11. The pharmaceutical composition according to any one of claims 1 to 10, wherein the sugar is sucrose.

12. The pharmaceutical composition according to claim 11, wherein the sucrose is present in an amount of about 2% (w / v) to about 4% (w / v).

13. The pharmaceutical composition according to any one of claims 1 to 12, wherein the protein excipient is recombinant human serum albumin, non-recombinant human serum albumin, or a combination thereof.

14. The pharmaceutical composition according to any one of claims 1 to 13, wherein the protein excipient is unrecombinant human serum albumin.

15. The pharmaceutical composition according to claim 13 or 14, wherein the non-recombinant human serum albumin is USP-grade non-recombinant human serum albumin.

16. The aforementioned non-recombinant human serum albumin was present in approximately 0.1% (w / v), 0.2% (w / v), 0.3% (w / v), 0.4% (w / v), 0.5% (w / v), 0.6% (w / v), 0.7% (w / v), 0.8% (w / v), 0.9% (w / v), 1% (w / v), 1.1% (w / v), 1.2% (w / v), 1.3% (w / v), 1.4% (w / v), 1.5% (w / v), and 1.6% (w / v). The pharmaceutical composition according to any one of claims 13 to 15, which is present in an amount of approximately 1.7% (w / v), approximately 1.8% (w / v), approximately 1.9% (w / v), approximately 2.0% (w / v), approximately 2.1% (w / v), approximately 2.2% (w / v), approximately 2.3% (w / v), approximately 2.4% (w / v), approximately 2.5% (w / v), approximately 2.6% (w / v), approximately 2.7% (w / v), approximately 2.8% (w / v), approximately 2.9% (w / v), or approximately 3.0% (w / v).

17. The pharmaceutical composition according to any one of claims 1 to 16, wherein the lentiviral vector is a VSV-G pseudotyped lentivirus.

18. The pharmaceutical composition according to claim 17, wherein the VSV-G pseudotyped lentivirus comprises a VSV-G polypeptide containing a mutation corresponding to the mutation at position 182 of SEQ ID NO:

2.

19. A pharmaceutical composition, (i) VSV-G pseudotype lentivirus and (ii) Approximately 10 mM to approximately 30 mM L-histidine buffer, (iii) Sodium chloride at a concentration of approximately 100 mM to approximately 400 mM, (iv) Approximately 1% (w / v) to approximately 5% (w / v) sucrose, (v) Contains approximately 0.1% (w / v) to approximately 2% (w / v) of unrecombinant human serum albumin, The pharmaceutical composition having a pH of about 5.5 to about 8.

0.

20. The aforementioned VSV-G pseudotype lentivirus is approximately 1.0E ＋０５ ~1.0E ＋０９ The pharmaceutical composition according to claim 19, present at a concentration of TU / mL.

21. The pharmaceutical composition according to claim 19 or 20, wherein the L-histidine is present at a concentration of about 15 to 25 mM, and the pharmaceutical composition has a pH of about 6 to about 7.

22. The pharmaceutical composition according to any one of claims 19 to 21, wherein the sodium chloride is present at a concentration of about 125 mM to about 175 mM.

23. The pharmaceutical composition according to any one of claims 19 to 22, wherein the sucrose is present in an amount of about 2% (w / v) to about 5% (w / v).

24. The pharmaceutical composition according to any one of claims 19 to 23, wherein the non-recombinant human serum albumin is present in an amount of about 0.1% (w / v) to about 1.5% (w / v).

25. The pharmaceutical composition according to any one of claims 19 to 24, wherein the non-recombinant human serum albumin is USP-grade non-recombinant human serum albumin.

26. The pharmaceutical composition according to any one of claims 19 to 25, wherein the VSV-G pseudotyped lentivirus comprises a VSV-G polypeptide containing a mutation corresponding to the mutation at position 182 of SEQ ID NO:

2.

27. The pharmaceutical composition according to claim 26, wherein the VSV-G polypeptide comprises mutations I182A, I182D, or I182E compared to SEQ ID NO:

2.

28. The pharmaceutical composition according to claim 26 or 27, wherein the VSV-G polypeptide comprises at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% of the sequence of SEQ ID NO:

4.

29. The pharmaceutical composition according to claim 26 or 27, wherein the VSV-G polypeptide comprises at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% of the sequence of Sequence ID No.

5.

30. The pharmaceutical composition according to any one of claims 26 to 29, wherein the VSV-G polypeptide further comprises mutations corresponding to the mutations at position 214 and / or 352 of SEQ ID NO:

2.

31. The pharmaceutical composition according to claim 30, wherein the VSV-G polypeptide includes substitutions at positions I182, T214, and T352 of SEQ ID NO:

2.

32. The pharmaceutical composition according to claim 30 or 31, wherein the substitution at position 182 of the VSV-G polypeptide is I182D or I182E, the substitution at position 214 of the VSV-G polypeptide is T214N, and the substitution at position 352 of the VSV-G polypeptide is T352A.

33. The pharmaceutical composition according to any one of claims 30 to 32, wherein the VSV-G polypeptide comprises the sequence of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, or SEQ ID NO:

25.

34. A pharmaceutical composition, (i) A VSV-G pseudotyped lentivirus comprising a VSV-G polypeptide containing mutations corresponding to the mutations at positions 182, 214, and / or 352 of Sequence ID No. 2, (ii) L-histidine buffer solution at a concentration of approximately 10 mM to approximately 30 mM, (iii) Sodium chloride at a concentration of approximately 100 mM to approximately 400 mM, (iv) Approximately 1% (w / v) to approximately 5% (w / v) of sucrose, (v) Contains approximately 0.1% (w / v) to approximately 2% (w / v) of unrecombinant human serum albumin, The pharmaceutical composition having a pH of about 6.5 to about 7.

5.

35. The pharmaceutical composition according to any one of claims 1 to 34, wherein the lentiviral vector further comprises a target-directing portion.

36. The pharmaceutical composition according to claim 35, wherein the target-directing portion is bound to CD7.

37. The pharmaceutical composition according to claim 36, wherein the target-directing portion comprises a polypeptide comprising: (i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 30, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 31, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 32, or any variant of the above; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 33, the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 34, and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 35, or any variant of the above.

38. The pharmaceutical composition according to claim 36 or 37, wherein the target-directing portion comprises a heavy chain variable region (VH) containing the amino acid sequence of SEQ ID NO: 42 and a light chain variable region (VL) containing the amino acid sequence of SEQ ID NO:

43.

39. The pharmaceutical composition according to any one of claims 36 to 38, wherein the target-directing portion comprises an antigen-binding domain having the amino acid sequence of SEQ ID NO: 44 or SEQ ID NO:

45.

40. The targeting moiety is T-S １ The formula includes the following, where T is the target binding domain and S １ However, the handle portion is the handle portion S. １ The pharmaceutical composition according to any one of claims 35 to 39, which is bound to the surface of the viral vector via a pharmacokinetic agent.

41. the handle portion S １ is L １ -Fc-L ２ -X １ and includes the formula of, in the formula L １ However, it is either a linker or does not exist. Fc is a variant Fc protein, L ２ However, it is either a linker or does not exist. X １ However, it is a polypeptide that contains a transmembrane domain, The above formula T-S １ The target-directing portion having T-L １ -Fc-L ２ -X １ A pharmaceutical composition according to claim 40, having the formula:

42. X １ However, ECD-T Ｍ - Containing a polypeptide having the formula ICD, in the formula, ECD is either the extracellular domain of a cell surface protein or a fragment thereof, or it is absent. T Ｍ However, it is the transmembrane domain of a transmembrane protein. ICD is either a protein or intracellular domain that facilitates the incorporation of the target-directing portion into the envelope of the viral particle, or it is absent. Said T-L １ -Fc-L ２ -X １ The target-directing portion having the formula T-L １ -Fc-L ２ -ECD-T Ｍ - The pharmaceutical composition according to claim 41, having the formula ICD.

43. T contains the amino acid sequence of SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 62, or SEQ ID NO:

63. L １ However, it contains the amino acid sequence of sequence number 72, Fc contains the amino acid sequence of SEQ ID NO: 82, L ２ However, it does not exist. ECD contains the amino acid sequence of SEQ ID NO: 83, T Ｍ However, it contains the amino acid sequence of sequence number 84, The pharmaceutical composition according to claim 42, wherein the ICD comprises an amino acid sequence containing an env embedded motif, and the env embedded motif comprises the amino acid sequence of SEQ ID NO:

85.

44. Said T-S １ The pharmaceutical composition according to claim 40, wherein the target-directing portion including the formula comprises an amino acid sequence having at least 90% identity with SEQ ID NO:

89.

45. The pharmaceutical composition according to any one of claims 1 to 44, wherein the lentiviral vector further comprises a nucleic acid molecule encoding a target heterologous molecule.

46. The pharmaceutical composition according to claim 45, wherein the aforementioned heterogeneous molecule is a chimeric antigen receptor ("CAR").

47. The pharmaceutical composition according to claim 46, wherein the CAR comprises an antigen-binding domain containing an antibody or a fragment thereof.

48. The pharmaceutical composition according to claim 47, wherein the antigen-binding domain of the CAR is bound to CD20.

49. The pharmaceutical composition according to claim 48, wherein the antigen-binding domain that binds to the CD20 comprises a heavy chain variable region having at least 90% identity with the amino acid sequence of SEQ ID NO: 73 and a light chain variable region having at least 90% identity with the amino acid sequence of SEQ ID NO: 74, and comprises a polypeptide comprising the light chain and the heavy chain.

50. The pharmaceutical composition according to claim 48 or 49, wherein the antigen-binding domain that binds to the CD20 comprises the amino acid sequence of SEQ ID NO: 75 or SEQ ID NO:

76.

51. The pharmaceutical composition according to any one of claims 48 to 50, wherein the CAR comprises an amino acid sequence having at least 90% identity with SEQ ID NO:

90.

52. A method for infecting cells, comprising contacting the cells with a pharmaceutical composition according to any one of claims 1 to 51.

53. A method for delivering a target heterologous molecule to a cell, the method comprising contacting the cell with a pharmaceutical composition according to any one of claims 1 to 51, wherein the lentiviral vector of the pharmaceutical composition comprises a nucleic acid molecule encoding the target heterologous molecule.

54. A method for delivering a target heterogeneous molecule, the method comprising administering a virus particle according to any one of claims 1 to 51 to the target, wherein the lentiviral vector of the pharmaceutical composition comprises a nucleic acid molecule encoding the target heterogeneous molecule.

55. A method for treating a disease or disorder in a subject, the method comprising administering to the subject a pharmaceutical composition according to any one of claims 1 to 51, wherein the lentiviral vector of the pharmaceutical composition comprises a nucleic acid molecule encoding a target heterogeneous molecule for treating the disease or disorder.

56. A method for delivering a heterologous molecule to a target cell, the method comprising contacting the cell with a pharmaceutical composition according to any one of claims 1 to 51, wherein the lentiviral vector of the pharmaceutical composition comprises a nucleic acid molecule encoding the heterologous molecule.

57. A pharmaceutical composition according to any one of claims 1 to 51, for use in the treatment of cancer, immune disorders, autoimmune disorders, or metabolic disorders.

58. Use of the pharmaceutical composition according to any one of claims 1 to 51 for the manufacture of a pharmaceutical for the treatment of cancer, an immune disorder, an autoimmune disorder, or a metabolic disorder.

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