Enhanced DNA dendrimers and methods of use thereof

Abstract

The embodiments provide compositions comprising DNA dendrimers, targeting molecules, therapeutic agents, adaptor molecules, support molecules, or combinations thereof. Pharmaceutical compositions, kits, and methods using and producing the same are also provided.

Description

[0001] ENHANCED DNA DENDRIMERS AND METHODS OF USE THEREOF

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to U.S. Provisional Application No. 63 / 518,457, filed on August 9, 2023, which is hereby incorporated by reference in its entirety.

[0004] REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0005] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on August 2, 2024, is named “COB-015WO_SL” and is 51,965 bytes in size.

[0006] FIELD

[0007] The present embodiments relate to DNA dendrimers and other molecules linked to, or encoding, targeting molecules, cargo molecules, adaptor molecules, support molecules, or combinations thereof, and methods of using and producing the same.

[0008] BACKGROUND

[0009] In many research, diagnostic, and therapeutic applications, the targets of action of a molecule, such as a reporter probe, a small molecule drug, a peptide or a nucleic acid, are intracellular. For nucleic acids that require transcription and / or translation inside a target cell, the nucleic acid must be transported safety into the cell nucleus. However, targeting of a molecule to selected cell types, achieving intracellular delivery to the cytosol and subsequent trafficking to the desired intracellular compartments such as the nucleus represent a challenging goal. Further, therapeutic nucleic acid cargo must be kept safe from degradation, and must express in the nucleus in quantities that are neither too limited or too much. Thus, there is a need for compositions that can reliably deliver molecule such as therapeutic nucleic acids to the nucleus of a target cell without degradation, and with the ability to optimize expression. The present disclosure addresses this need and others.

[0010] SUMMARY

[0011] In some embodiments, a composition is provided, the composition comprising a DNA dendrimer, a targeting moiety, and an adaptor molecule-cargo polynucleotide complex. In some embodiments, the cargo polynucleotide comprises at least one promoter and at least one coding sequence encoding for at least one molecule of interest. In some embodiments, cargo polynucleotide is a nicked circular polynucleotide, a linear polynucleotide with a closed 5' and 3' end, a linear polynucleotide with open 5' and 3' ends, or a linear polynucleotide with one open and one closed end, wherein the one open and one closed end can be at either the 5' and 3' of the polynucleotide.

[0012] In some embodiments, the cargo polynucleotide further comprises at least one DNA targeting sequence (DTS).

[0013] In some embodiments, the cargo polynucleotide further comprises at least one nuclear localization signal (NLS).

[0014] In some embodiments, the cargo polynucleotide comprises at least one DTS and at least one NLS.

[0015] In some embodiments, the adaptor molecule comprises a DNA dendrimer binding sequence (DBS) and a cargo binding region (CBR). In some embodiments, the DBS comprises a nucleic acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 3, 4, 10, 11, 22, or 23.

[0016] In some embodiments, the CBR is linked or conjugated to the cargo polynucleotide by DNA ligation. In some embodiments, the CBR is linked or conjugated to the cargo polynucleotide by chemical coupling.

[0017] In some embodiments, the adaptor molecule further comprises at least one NLS. In some embodiments, the at least one NLS comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NO: 1, 2, 15, or 43.

[0018] In some embodiments, the at least one NLS further comprises at least one spacer located before or after the at least one NLS. In some embodiments, the at least one spacer comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NO: 5 or 29.

[0019] In some embodiments, the adaptor molecule further comprises at least one DTS. In some embodiments, the adaptor molecule further comprises a cell penetrating peptide sequence (CPP). In some embodiments, the CPP comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 6.

[0020] In some embodiments, the adaptor molecule further comprises at least one cleavage site. In some embodiments, the cleavage site is a val-cit linker.

[0021] In some embodiments, the adaptor molecule further comprises at least one flexible linker. In some embodiments, the at least one flexible linker is polyethylene glycol (PEG), propylene glycol alginate (PGA), PEG-polylactic acid (PLA), poly lactic-co-glycolic acid (PGLA), (GG)n, (GGGGS)n, or (GGGGA)n, wherein each n is, independently, 1-5.

[0022] In some embodiments, the composition further comprises a support molecule. In some embodiments, the support molecule comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NO: 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48. In some embodiments, the support molecule further comprises a PEG molecule linked or conjugated at the N-terminus or C-terminus of the support molecule. In some embodiments, the PEG molecule is PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000.

[0023] In some embodiments, the support molecule comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 19. In some embodiments, the support molecule further comprises a PEG molecule linked or conjugated at the N-terminus or C- terminus of the support molecule. In some embodiments, the PEG molecule is PEG2000.

[0024] In some embodiments, the support molecule comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 19 and PEG2000 conjugated at the N-terminus or C-terminus of SEQ ID NO: 19. In some embodiments, PEG2000 is conjugated at the N- terminus of SEQ ID NO: 19. In some embodiments, PEG2000 is conjugated at the C- terminus of SEQ ID NO: 19. In some embodiments, the support molecule comprises the sequence of SEQ ID NO:

[0025] 30.

[0026] In some embodiments, the targeting moiety is an antibody, a naturally-occurring ligand for the receptor or a functional derivative thereof, a vitamin, a hormone, a small molecule mimetic of a naturally-occurring ligand, a peptide, a polypeptide, a peptidomimetic, a carbohydrate, a lipid, an aptamer, a nucleic acid, a toxin, a component of a microorganism, any other molecule provided it binds specifically to the cell surface molecule and induces endocytosis of the bound moiety, or any combination thereof.

[0027] In some embodiments, a composition is provided, the composition comprising a cargo polynucleotide, a support molecule, and a DNA dendrimer linked to a targeting moiety. In some embodiments, the support molecule is as provided for herein. In some embodiments, the targeting moiety is as provided for herein.

[0028] In some embodiments, the cargo polynucleotide comprises at least one promoter and at least one coding sequence encoding for at least one molecule of interest. In some embodiments, the cargo polynucleotide optionally comprises a DBS. In some embodiments, the cargo polynucleotide is a full circular polynucleotide (e.g., plasmid), nicked circular polynucleotide, a linear polynucleotide with closed 5' and 3' end, a linear polynucleotide with open 5' and 3' ends, or a linear polynucleotide with one open and one closed end, wherein the one open and one closed end can be at either the 5' and 3' of the cargo polynucleotide.

[0029] In some embodiments, the cargo polynucleotide further comprises at least one DTS.

[0030] In some embodiments, the cargo polynucleotide further comprises at least one NLS.

[0031] In some embodiments, the cargo polynucleotide comprises at least one DTS and at least one NLS.

[0032] In some embodiments, the cargo polynucleotide comprises a DBS, wherein the DBS comprises a nucleic acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NO: 3, 4, 10, 11, 22, or 23.

[0033] In some embodiments, the support molecule comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NO: 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48. In some embodiments, the support molecule further comprises a PEG molecule linked or conjugated at the N-terminus or C-terminus of the support molecule. In some embodiments, the PEG molecule is PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000.

[0034] In some embodiments, the support molecule comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 19. In some embodiments, the support molecule further comprises a PEG molecule linked or conjugated at the N-terminus or C- terminus of the support molecule. In some embodiments, the PEG molecule is PEG2000.

[0035] In some embodiments, the support molecule comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 19 and PEG2000 conjugated at the N-terminus or C-terminus of SEQ ID NO: 19. In some embodiments, PEG2000 is conjugated at the N- terminus of SEQ ID NO: 19. In some embodiments, PEG2000 is conjugated at the C- terminus of SEQ ID NO: 19.

[0036] In some embodiments, the support molecule comprises the sequence of SEQ ID NO: 30.

[0037] In some embodiments, any of the compositions provided for herein may comprise a nitrogen / phosphate (N / P) ratio within a set threshold. In some embodiments, the N / P ratio is between 0.5 and 10. In some embodiments, the N / P ratio is between 2 and 5.

[0038] In some embodiments, a pharmaceutical composition is provided comprising a composition as provided for herein and a pharmaceutically acceptable carrier.

[0039] In some embodiments, a method of delivering a molecule of interest to the nucleus of a target cell is provided, the method comprising contacting the target cell with a composition or pharmaceutical composition as provided for herein, wherein the targeting moiety binds to the target cell.

[0040] In some embodiments, a method of treating a disease is provided, the method comprising administering a composition or pharmaceutical composition as provided for herein to a subject to treat the disease, wherein the targeting moiety binds to the target cell.

[0041] In some embodiments, a plasmid is provided, the plasmid comprising a plasmid backbone comprising at least two enzyme restriction recognition sites, at least one promoter, at least one coding sequence for at least one molecule of interest, and, optionally, a DBS. In some embodiments, the plasmid is capable of forming a cargo polynucleotide with various structures depending on whether the plasmid has one or more, or none of, a 5' end and a 3' end. In some embodiments, the plasmid is a full circular polynucleotide, a nicked circular nucleotide, a linear nucleotide with a closed 5’ and 3’ end, a linear nucleotide with open 5’ and 3’ ends, or a linear nucleotide with one open and one closed end.

[0042] In some embodiments, the plasmid further comprises at least one DTS.

[0043] In some embodiments, the plasmid further comprises at least one NLS.

[0044] In some embodiments, the plasmid comprises at least one DTS and at least one NLS.

[0045] In some embodiments, the DBS is present and comprises a nucleic acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NO: 3, 4, 10, 11, 22, or 23.

[0046] In some embodiments, a method of manufacturing a composition as provided for herein is provided, the method comprising contacting a plasmid as provided for herein with one or more restriction enzymes that cut at the restriction enzyme recognition sites to form a nicked circular polynucleotide, a linear polynucleotide with a closed 5' and 3' end, a linear polynucleotide with open 5' and 3' ends, or a linear polynucleotide with one open and one closed end, linking the cargo polynucleotide to the adaptor molecule to form an adaptor molecule-cargo polynucleotide complex, and linking the adaptor molecule- cargo polynucleotide complex and a targeting moiety to a DNA dendrimer to form the composition.

[0047] In some embodiments, a method of manufacturing a composition as provided for herein is provided, the method comprising contacting a plasmid as provided for herein that comprises a DNA dendrimer binding sequence (DBS) with one or more restriction enzymes that cut at the restriction enzyme recognition sites to form a nicked circular polynucleotide, a linear polynucleotide with a closed 5' and 3' end, a linear polynucleotide with open 5' and 3' ends, or a linear polynucleotide with one open and one closed end, and linking the cargo polynucleotide and a targeting moiety to a DNA dendrimer to form the composition.

[0048] In some embodiments, a method of manufacturing a composition as provided for herein is provided, the method comprising contacting a circular uncut plasmid as provided for herein with a DNA dendrimer linked to a targeting moiety with a support molecule capable of condensing the size of the cargo polynucleotide and the DNA dendrimer, such that the cargo polynucleotide and the DNA dendrimer are associated together to form the composition.

[0049] In some embodiments, a kit is provided, the kit comprising a composition as provided for herein, a pharmaceutical composition as provided for herein, a plasmid as provided for herein, or any combination thereof. BRIEF DESCRIPTION OF THE FIGURES

[0050] FIG. 1 depicts a diagram showing a plasmid map, and individual topologies the plasmid can be changed into by contacting or not contacting certain restriction enzymes with the plasmid.

[0051] FIG. 2 depicts GFP fluorescence percentages for various polynucleotide topologies.

[0052] FIG. 3 depicts a graph showing the number of GFP positive cells per unit area for various polynucleotide topologies.

[0053] FIG. 4 depicts relative mean fluorescence of a polynucleotide containing a DNA targeting sequence (DTS) compared to a polynucleotide without a DTS in CH0-K1 cells.

[0054] FIG. 5 depicts relative mean fluorescence of a polynucleotide containing a DNA targeting sequence (DTS) compared to a polynucleotide without a DTS in A427 cells.

[0055] FIG. 6 depicts relative mean fluorescence of a polynucleotide containing a DNA targeting sequence (DTS) compared to a polynucleotide without a DTS in C2C12 cells.

[0056] FIG. 7 depicts relative integral fluorescence of a polynucleotide containing a DNA targeting sequence (DTS) compared to a polynucleotide without a DTS in C2C12 cells.

[0057] FIG. 8 depicts relative peak fluorescence of a polynucleotide containing a DNA targeting sequence (DTS) compared to a polynucleotide without a DTS in C2C12 cells.

[0058] FIG. 9A-FIG. 9D shows brightfield and GFP imaging of HepG2 cells 48 hours posttransfection a Genl A Control plasmid (FIG. 9A); a Genl B Control plasmid (FIG. 9B); a Gen3 a(-) plasmid (FIG. 9C); and a Gen3 c(-) plasmid (FIG. 9D).

[0059] FIG. 10 illustrates the total fluorescent signal (integrated density) for HepG2 cells transfected with various plasmids after 48 hours.

[0060] FIG. 11 shows results of a cell titer gio assay using 0.2 ug of plasmid per well.

[0061] FIG. 12 shows results of a cell titer gio assay using 1 ug of plasmid per well.

[0062] FIG. 1 a illustrates the ability of various support molecules provided for herein to complex a nucleotide cargo. FIG. 13b illustrates the ability of various support molecules provided for herein to protect a nucleotide cargo from DNAse 1 degradation.

[0063] FIG. 14a illustrates the ability of various support molecules provided for herein to complex a nucleotide cargo. FIG. 14b illustrates the ability of various support molecules provided for herein to protect a nucleotide cargo from DNAse 1 degradation.

[0064] FIG. 15a illustrates the ability of various support molecules provided for herein to complex a nucleotide cargo. FIG. 15b illustrates the ability of various support molecules provided for herein to protect a nucleotide cargo from DNAse 1 degradation. FIG. 16a illustrates the ability of blends of various support molecules provided for herein to complex a nucleotide cargo. FIG. 14b illustrates the ability of blends of various support molecules provided for herein to protect a nucleotide cargo from DNAse 1 degradation.

[0065] DETAILED DESCRIPTION

[0066] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing, suitable methods and materials are described herein. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting. Other features and advantages of the embodiments provided for herein will be apparent from the present detailed description and claims.

[0067] The techniques and procedures for recombinant manipulations, including nucleic acid and peptide synthesis, are generally performed according to conventional methods in the art and various general references (e.g., Sambrook et al, 2001, Molecular Cloning, A Laboratory Approach, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.; Ausubel et al., eds, 2005, Current Protocols in Molecular Biology, John Wiley & Sons, New York, N.Y.; and Gerhardt et al., eds., 1994, Methods for General and Molecular Bacteriology, American Society for Microbiology, Washington, D.C.), which are provided throughout this document.

[0068] The term “about” or “approximately” means plus or minus 10% of the numerical value of the number with which it is being used. Therefore, about 50% means in the range of 45%-55%.

[0069] The singular forms “a”, “an”, and “the” include plural reference unless the context clearly dictates otherwise.

[0070] The terms “comprise,” “have,” and “include” and their conjugates, as used herein, mean “including but not limited to.” While various compositions, methods, and devices are described in terms of “comprising” various components or steps (interpreted as meaning “including, but not limited to”), the compositions, methods, and devices can also “consist essentially of’ or “consist of’ the various components and steps.

[0071] The term “antibody,” as used herein, refers to an immunoglobulin molecule which can specifically bind to a specific epitope on an antigen. Antibodies can be intact immunoglobulins derived from natural sources or from recombinant sources and can be immunoreactive portions of intact immunoglobulins. The antibodies useful in the present invention may exist in a variety of forms including, for example, polyclonal antibodies, monoclonal antibodies, intracellular antibodies (“intrabodies”), Fv, Fab and F(ab)2, as well as single chain antibodies (scFv), camelid antibodies and humanized antibodies (Harlow et al., 1999, Using Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, NY; Harlow et al., 1989, Antibodies: A Laboratory Manual, Cold Spring Harbor, N.Y.; Houston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; Bird et al., 1988, Science 242:423-426).

[0072] “Complementary” as used herein refers to the broad concept of subunit sequence complementarity between two nucleic acids, e.g., two DNA molecules. When a nucleotide position in both of the molecules is occupied by nucleotides normally capable of base pairing with each other, then the nucleic acids are considered to be complementary to each other at this position. Thus, two nucleic acids are substantially complementary to each other when at least about 50%, preferably at least about 60% and more preferably at least about 80% of corresponding positions in each of the molecules are occupied by nucleotides which normally base pair with each other (e.g., A:T and G:C nucleotide pairs).

[0073] As used herein, a “DNA-based carrier” refers to a delivery system that comprises a deoxyribonucleic acid molecule. A non-limiting example of a DNA-based carrier is a DNA dendrimer. Other DNA-based carriers include double- stranded DNA, single-stranded DNA, and single-stranded hairpin DNA, or multimers thereof.

[0074] As used herein, a “DNA dendrimer” or “dendrimer” refers to a matrix of polynucleotides, exhibiting branching, formed by the sequential or generational addition of branched layers to or from a core molecule, such as an initiating monomer.

[0075] As used herein, an “initiating monomer” is a polynucleotide compound that serves to nucleate the formation of a dendrimer.

[0076] As used herein, an “extending monomer” is a polynucleotide compound that can bind to the initiating monomer and / or to each other during assembly of a dendrimer. Extending monomers form the layers of the dendrimer. The first layer of a dendrimer is the layer of extending monomers closest to the initiating monomer. The outer layer is the layer furthest from the initiating monomer and forming the surface of the dendrimer. Extending monomers are also referred to in the art as matrix monomers, matrix extending monomers and matrix polynucleotide monomers.

[0077] The terms “substituting,” “substituted,” “mutating,” or “mutated” as used herein refer to altering, deleting, or inserting one or more amino acids or nucleotides in a polypeptide or polynucleotide sequence to generate a variant of that sequence. The terms “polynucleotide” or “nucleic acid molecule” means a molecule comprising a chain of nucleotides covalently linked by a sugar-phosphate backbone or other equivalent covalent chemistry. Double and single- stranded DNAs and RNAs are non-limiting examples of polynucleotides.

[0078] The term “polypeptide” or “protein” means a molecule that comprises at least two amino acid residues linked by a peptide bond to form a polypeptide. In some embodiments, the term “peptide” can also be used.

[0079] The term “variant” as used herein refers to a polypeptide or polynucleotide that differs from a reference polypeptide or a reference polynucleotide by one or more modifications, including substitutions, insertions, or deletions.

[0080] Conventional notation is used herein to describe polynucleotide sequences: the lefthand end of a single-stranded polynucleotide sequence is the 5 '-end; the left-hand direction of a double-stranded polynucleotide sequence is referred to as the 5 '-direction.

[0081] As used herein, the term “promoter / regulatory sequence” means a nucleic acid sequence which controls or facilitates the expression of a gene product operably linked to the promoter / regulator sequence. In some instances, this sequence may be the core promoter sequence and in other instances, this sequence may also include an enhancer sequence and other regulatory elements which control or facilitate the expression of the gene product. The promoter / regulatory sequence may, for example, be one which expresses the gene product in an inducible manner. An “inducible” promoter is a nucleotide sequence which, when operably linked with a polynucleotide that encodes or specifies a gene product, causes the gene product to be produced substantially only when an inducer which corresponds (e.g., binds) to the promoter is present.

[0082] As used herein, a “targeting moiety” refers to a molecule that binds to a molecule present on the cell surface of a target cell.

[0083] As used herein, a “targeted DNA-based carrier” and “a DNA-based carrier comprising a targeting moiety” refers to a composition comprising a DNA-based carrier and a targeting moiety. The targeting moiety may be linked directly, or by means of a linker, to the DNA- based carrier. Alternatively, the targeting moiety may be linked to another molecule, such as a cargo molecule or a secondary, non-nucleic acid carrier in the composition. The DNA- based carrier is targeted by virtue of being present in the same composition with the targeted cargo or targeted secondary carrier.

[0084] The term “vector” as used herein refers to a nucleic acid which can infect, transfect, transiently or permanently transduce a cell. It will be recognized that a vector can be a naked nucleic acid, or a nucleic acid complexed with protein or lipid. Vectors include, but are not limited to, replicons (such as RNA replicons, bacteriophages) to which fragments of DNA may be attached and become replicated. Vectors thus include, but are not limited to RNA, autonomous self-replicating circular or linear DNA or RNA (i.e., “plasmids”), and include both the expression and non-expression plasmids. Where a recombinant microorganism or cell culture is described as hosting an “expression vector” this includes both extra- chromosomal circular and linear DNA and DNA that has been incorporated into the host chromosome(s). Where a vector is being maintained by a host cell, the vector may either be stably replicated by the cells during mitosis as an autonomous structure or is incorporated within the host’s genome.

[0085] “Promoter” as used herein means a synthetic or naturally-derived molecule which is capable of conferring, activating or enhancing expression of a nucleic acid in a cell. A promoter can comprise one or more specific transcriptional regulatory sequences to further enhance expression and / or to alter the spatial expression and / or temporal expression of same. A promoter can also comprise distal enhancer or repressor elements, which can be located as much as several thousand base pairs from the start site of transcription. Such promoterenhancers can modify, for example, but not limited to, tissue specificity or transduction efficiency. A promoter can be derived from sources including viral, bacterial, fungal, plants, insects, and animals. A promoter can regulate the expression of a gene component constitutively, or differentially with respect to cell, the tissue or organ in which expression occurs or, with respect to the developmental stage at which expression occurs, or in response to external stimuli such as physiological stresses, pathogens, metal ions, or inducing agents.

[0086] The term “topology” as used herein refers to different structural arrangement of any vector, plasmid, or polynucleotide disclosed herein. For example, polynucleotides can have a circular topology, such as a plasmid, where the polynucleotide has no 5’ or 3’ end. Polynucleotides disclosure herein can also have linear topologies, where the polynucleotide has a 5’ and 3’ end. Polynucleotides with a liner topology may have one or both ends of the polynucleotide covalently closed. In some embodiments, certain restriction enzymes can covalently close a DNA end, for example, TelN Protelomerase.

[0087] Compositions

[0088] A. DNA-Based Carriers In some embodiments, compositions disclosed herein comprise a DNA-based carrier. DNA-based carriers include, but are not limited to, DNA dendrimers, double- stranded linear DNA, single- stranded linear DNA, and single- stranded hairpin DNA, formulated either as monomolecular structures or including several units of the conformation cross-linked together (e.g., multimers). In some embodiments, the composition comprises a DNA dendrimer. DNA dendrimers are spheroid particles (diameter typically about 130 to about 150 nm, although they can be designed to be other sizes) of flexible branches formed by inter-hybridized DNA monomers. Each DNA monomer is composed of two polynucleotide strands that share a central region of complementary sequences where the two strands hybridize to each other forming a double-stranded region, leaving 4 terminal single-stranded polynucleotide portions. These terminal sequences are complementary among themselves; hence, they can hybridize (in layers) to terminal sequences of other DNA monomers. Optionally, DNA dendrimers comprise covalently cross-linked strands of DNA.

[0089] The double-stranded region formed by the region of complementary sequence between the first and second oligonucleotides is from about 4 to about 2000 bases in length. In some embodiments, the double- stranded region is from about 5 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 6 to about 2000 bases in length. In some embodiments, the double- stranded region is from about 7 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 8 to about 2000 bases in length. In some embodiments, the double- stranded region is from about 9 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 10 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 15 to about 2000 bases in length. In some embodiments, the double- stranded region is from about 20 to about 2000 bases in length. In some embodiments, the doublestranded region is from about 25 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 30 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 35 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 40 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 45 to about 2000 bases in length. In some embodiments, the double- stranded region is from about 50 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 60 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 70 to about 2000 bases in length. In some embodiments, the double- stranded region is from about 80 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 90 to about 2000 bases in length. In some embodiments, the double- stranded region is from about 100 to about 2000 bases in length. In some embodiments, the doublestranded region is from about 200 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 300 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 400 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 500 to about 2000 bases in length. In some embodiments, the double-stranded region is from about 1000 to about 2000 bases in length. In some embodiments, the double- stranded region is from about 1500 to about 2000 bases in length.

[0090] In some embodiments, the double-stranded region is from about 4 to about 1500 bases in length. In some embodiments, the double-stranded region is from about 4 to about 1000 bases in length. In some embodiments, the double- stranded region is from about 4 to about 500 bases in length. In some embodiments, the double-stranded region is from about 4 to about 400 bases in length. In some embodiments, the double- stranded region is from about 4 to about 300 bases in length. In some embodiments, the double- stranded region is from about 4 to about 200 bases in length. In some embodiments, the double-stranded region is from about 4 to about 100 bases in length. In some embodiments, the double- stranded region is from about 4 to about 90 bases in length. In some embodiments, the double- stranded region is from about 4 to about 80 bases in length. In some embodiments, the double-stranded region is from about 4 to about 70 bases in length. In some embodiments, the double- stranded region is from about 4 to about 60 bases in length. In some embodiments, the double-stranded region is from about 4 to about 50 bases in length. In some embodiments, the double-stranded region is from about 4 to about 45 bases in length. In some embodiments, the double-stranded region is from about 4 to about 40 bases in length. In some embodiments, the double- stranded region is from about 4 to about 35 bases in length. In some embodiments, the double- stranded region is from about 4 to about 30 bases in length. In some embodiments, the double- stranded region is from about 4 to about 25 bases in length. In some embodiments, the double- stranded region is from about 4 to about 20 bases in length. In some embodiments, the double- stranded region is from about 4 to about 15 bases in length. In some embodiments, the double- stranded region is from about 4 to about 10 bases in length. In some embodiments, the double- stranded region is from about 4 to about 9 bases in length. In some embodiments, the double- stranded region is from about 4 to about 8 bases in length. In some embodiments, the double- stranded region is from about 4 to about 7 bases in length. In some embodiments, the double- stranded region is from about 4 to about 6 bases in length. In some embodiments, the double- stranded region is from about 4 to about 5 bases in length.

[0091] In some embodiments, the double-stranded region is from about 5 to about 200 bases in length. In some embodiments, the double-stranded region is from about 6 to about 200 bases in length. In some embodiments, the double-stranded region is from about 7 to about 200 bases in length. In some embodiments, the double-stranded region is from about 8 to about 200 bases in length. In some embodiments, the double-stranded region is from about 9 to about 200 bases in length. In some embodiments, the double- stranded region is from about 10 to about 200 bases in length. In some embodiments, the double- stranded region is from about 11 to about 200 bases in length. In some embodiments, the double-stranded region is from about 12 to about 200 bases in length. In some embodiments, the double- stranded region is from about 13 to about 200 bases in length. In some embodiments, the doublestranded region is from about 14 to about 200 bases in length. In some embodiments, the double-stranded region is from about 15 to about 200 bases in length. In some embodiments, the double-stranded region is from about 20 to about 200 bases in length. In some embodiments, the double-stranded region is from about 25 to about 200 bases in length. In some embodiments, the double- stranded region is from about 30 to about 200 bases in length. In some embodiments, the double- stranded region is from about 35 to about 200 bases in length. In some embodiments, the double-stranded region is from about 40 to about 200 bases in length. In some embodiments, the double- stranded region is from about 45 to about 200 bases in length. In some embodiments, the double-stranded region is from about 50 to about 200 bases in length. In some embodiments, the double- stranded region is from about 60 to about 200 bases in length. In some embodiments, the double- stranded region is from about 70 to about 200 bases in length. In some embodiments, the double-stranded region is from about 80 to about 200 bases in length. In some embodiments, the double- stranded region is from about 90 to about 200 bases in length. In some embodiments, the doublestranded region is from about 100 to about 200 bases in length. In some embodiments, the double-stranded region is from about 125 to about 200 bases in length. In some embodiments, the double-stranded region is from about 150 to about 200 bases in length. In some embodiments, the double- stranded region is from about 175 to about 200 bases in length.

[0092] In some embodiments, the double-stranded region is from about 5 to about 175 bases in length. In some embodiments, the double-stranded region is from about 5 to about 150 bases in length. In some embodiments, the double- stranded region is from about 5 to about 125 bases in length. In some embodiments, the double-stranded region is from about 5 to about 100 bases in length. In some embodiments, the double- stranded region is from about 5 to about 90 bases in length. In some embodiments, the double- stranded region is from about 5 to about 80 bases in length. In some embodiments, the double-stranded region is from about 5 to about 70 bases in length. In some embodiments, the double-stranded region is from about 5 to about 60 bases in length. In some embodiments, the double-stranded region is from about 5 to about 50 bases in length. In some embodiments, the double-stranded region is from about 5 to about 45 bases in length. In some embodiments, the doublestranded region is from about 5 to about 40 bases in length. In some embodiments, the double-stranded region is from about 5 to about 35 bases in length. In some embodiments, the double-stranded region is from about 5 to about 30 bases in length. In some embodiments, the double-stranded region is from about 5 to about 25 bases in length. In some embodiments, the double-stranded region is from about 5 to about 20 bases in length. In some embodiments, the double- stranded region is from about 5 to about 15 bases in length. In some embodiments, the double- stranded region is from about 5 to about 14 bases in length. In some embodiments, the double- stranded region is from about 5 to about 13 bases in length. In some embodiments, the double-stranded region is from about 5 to about 12 bases in length. In some embodiments, the double- stranded region is from about 5 to about 11 bases in length. In some embodiments, the double-stranded region is from about 5 to about 10 bases in length. In some embodiments, the double- stranded region is from about 5 to about 9 bases in length. In some embodiments, the double-stranded region is from about 5 to about 8 bases in length. In some embodiments, the double- stranded region is from about 5 to about 7 bases in length. In some embodiments, the double- stranded region is from about 5 to about 6 bases in length.

[0093] In some embodiments, the double-stranded region is from about 25 to about 50 bases in length. In some embodiments, the double-stranded region is from about 26 to about 50 bases in length. In some embodiments, the double-stranded region is from about 27 to about 50 bases in length. In some embodiments, the double-stranded region is from about 28 to about 50 bases in length. In some embodiments, the double- stranded region is from about 29 to about 50 bases in length. In some embodiments, the double-stranded region is from about 30 to about 50 bases in length. In some embodiments, the double-stranded region is from about 31 to about 50 bases in length. In some embodiments, the double- stranded region is from about 32 to about 50 bases in length. In some embodiments, the double- stranded region is from about 33 to about 50 bases in length. In some embodiments, the double-stranded region is from about 34 to about 50 bases in length. In some embodiments, the double- stranded region is from about 35 to about 50 bases in length. In some embodiments, the double-stranded region is from about 36 to about 50 bases in length. In some embodiments, the double-stranded region is from about 37 to about 50 bases in length. In some embodiments, the double-stranded region is from about 38 to about 50 bases in length. In some embodiments, the double- stranded region is from about 39 to about 50 bases in length. In some embodiments, the double- stranded region is from about 40 to about 50 bases in length. In some embodiments, the double-stranded region is from about 45 to about 50 bases in length.

[0094] In some embodiments, the double-stranded region is from about 25 to about 45 bases in length. In some embodiments, the double-stranded region is from about 25 to about 40 bases in length. In some embodiments, the double-stranded region is from about 25 to about 39 bases in length. In some embodiments, the double-stranded region is from about 25 to about 38 bases in length. In some embodiments, the double-stranded region is from about 25 to about 37 bases in length. In some embodiments, the double- stranded region is from about 25 to about 36 bases in length. In some embodiments, the double- stranded region is from about 25 to about 35 bases in length. In some embodiments, the double- stranded region is from about 25 to about 34 bases in length. In some embodiments, the double-stranded region is from about 25 to about 33 bases in length. In some embodiments, the double-stranded region is from about 25 to about 32 bases in length. In some embodiments, the doublestranded region is from about 25 to about 31 bases in length. In some embodiments, the double-stranded region is from about 25 to about 30 bases in length. In some embodiments, the double-stranded region is from about 25 to about 29 bases in length. In some embodiments, the double-stranded region is from about 25 to about 28 bases in length. In some embodiments, the double-stranded region is from about 25 to about 27 bases in length. In some embodiments, the double- stranded region is from about 25 to about 26 bases in length.

[0095] In some embodiments, the double-stranded region is from about 25 to about 35 bases in length. In some embodiments, the double-stranded region is from about 26 to about 35 bases in length. In some embodiments, the double- stranded region is from about 27 to about 35 bases in length. In some embodiments, the double-stranded region is from about 28 to about 35 bases in length. In some embodiments, the double-stranded region is from about 29 to about 35 bases in length. In some embodiments, the double-stranded region is from about 30 to about 35 bases in length. In some embodiments, the double-stranded region is from about 31 to about 35 bases in length. In some embodiments, the double- stranded region is from about 32 to about 35 bases in length. In some embodiments, the double- stranded region is from about 33 to about 35 bases in length. In some embodiments, the double-stranded region is from about 34 to about 35 bases in length.

[0096] In some embodiments, the double-stranded region is 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 125, 150, 175, 200, or more than 200 bases in length or any length in-between any of the recited values. In some embodiments, the double-stranded region is 4 bases in length. In some embodiments, the double-stranded region is 5 bases in length. In some embodiments, the double- stranded region is 6 bases in length. In some embodiments, the double- stranded region is 7 bases in length. In some embodiments, the double-stranded region is 8 bases in length. In some embodiments, the double-stranded region is 9 bases in length. In some embodiments, the double-stranded region is 10 bases in length. In some embodiments, the double- stranded region is 11 bases in length. In some embodiments, the double- stranded region is 12 bases in length. In some embodiments, the double-stranded region is 13 bases in length. In some embodiments, the double-stranded region is 14 bases in length. In some embodiments, the double-stranded region is 15 bases in length. In some embodiments, the double-stranded region is 20 bases in length. In some embodiments, the double- stranded region is 21 bases in length. In some embodiments, the double-stranded region is 22 bases in length. In some embodiments, the double-stranded region is 23 bases in length. In some embodiments, the double-stranded region is 24 bases in length. In some embodiments, the double-stranded region is 25 bases in length. In some embodiments, the double- stranded region is 26 bases in length. In some embodiments, the double-stranded region is 27 bases in length. In some embodiments, the double-stranded region is 28 bases in length. In some embodiments, the double-stranded region is 29 bases in length. In some embodiments, the double- stranded region is 30 bases in length. In some embodiments, the double- stranded region is 31 bases in length. In some embodiments, the double-stranded region is 32 bases in length. In some embodiments, the double-stranded region is 33 bases in length. In some embodiments, the double-stranded region is 34 bases in length. In some embodiments, the double- stranded region is 35 bases in length. In some embodiments, the double- stranded region is 36 bases in length. In some embodiments, the double-stranded region is 37 bases in length. In some embodiments, the double-stranded region is 38 bases in length. In some embodiments, the double-stranded region is 39 bases in length. In some embodiments, the double- stranded region is 40 bases in length. In some embodiments, the double- stranded region is 41 bases in length. In some embodiments, the double-stranded region is 42 bases in length. In some embodiments, the double-stranded region is 43 bases in length. In some embodiments, the double-stranded region is 44 bases in length. In some embodiments, the double- stranded region is 45 bases in length. In some embodiments, the double- stranded region is 46 bases in length. In some embodiments, the double-stranded region is 47 bases in length. In some embodiments, the double-stranded region is 48 bases in length. In some embodiments, the double-stranded region is 49 bases in length. In some embodiments, the double- stranded region is 50 bases in length. In some embodiments, the double- stranded region is 55 bases in length. In some embodiments, the double-stranded region is 60 bases in length. In some embodiments, the double-stranded region is 65 bases in length. In some embodiments, the double-stranded region is 70 bases in length. In some embodiments, the double- stranded region is 75 bases in length. In some embodiments, the double- stranded region is 80 bases in length. In some embodiments, the double-stranded region is 85 bases in length. In some embodiments, the double-stranded region is 90 bases in length. In some embodiments, the double-stranded region is 95 bases in length. In some embodiments, the double- stranded region is 100 bases in length. In some embodiments, the double-stranded region is 125 bases in length. In some embodiments, the double-stranded region is 150 bases in length. In some embodiments, the double-stranded region is 175 bases in length. In some embodiments, the double-stranded region is 200 bases in length. In some embodiments, the double-stranded region is more than 200 bases in length.

[0097] Each single-stranded arm is each, independently, from about 4 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 5 to about 200 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 6 to about 200 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 7 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 8 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 9 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 10 to about 200 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 11 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 12 to about 200 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 13 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 14 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 15 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 20 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 25 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 30 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 35 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 40 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 45 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 50 to about 200 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 60 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 70 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 80 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 90 to about 200 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 100 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 125 to about 200 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 150 to about 200 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 175 to about 200 bases in length.

[0098] In some embodiments, each single-stranded arm is each, individually, from about 5 to about 175 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 5 to about 150 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 5 to about 125 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 5 to about 100 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 5 to about 90 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 5 to about 80 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 5 to about 70 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 5 to about 60 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 5 to about 50 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 5 to about 45 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 5 to about 40 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 5 to about 35 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 5 to about 30 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 5 to about 25 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 5 to about 20 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 5 to about 15 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 5 to about 14 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 5 to about 13 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 5 to about 12 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 5 to about 11 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 5 to about 10 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 5 to about 9 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 5 to about 8 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 5 to about 7 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 5 to about 6 bases in length.

[0099] In some embodiments, each single-stranded arm is each, individually, from about 5 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 6 to about 50 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 7 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 8 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 9 to about 50 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 10 to about 50 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 11 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 12 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 13 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 14 to about 50 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 15 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 16 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 17 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 18 to about 50 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 19 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 20 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 21 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 22 to about 50 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 23 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 24 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 25 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 30 to about 50 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 35 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 40 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 45 to about 50 bases in length.

[0100] In some embodiments, each single-stranded arm is each, individually, from about 25 to about 50 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 26 to about 50 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 27 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 28 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 29 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 30 to about 50 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 31 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 32 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 33 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 34 to about 50 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 35 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 36 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 37 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 38 to about 50 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 39 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 40 to about 50 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 45 to about 50 bases in length.

[0101] In some embodiments, each single-stranded arm is each, individually, from about 25 to about 45 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 25 to about 40 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 25 to about 39 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 25 to about 38 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 25 to about 37 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 25 to about 36 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 25 to about 35 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 25 to about 34 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 25 to about 33 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 25 to about 32 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 25 to about 31 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 25 to about 30 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 25 to about 29 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 25 to about 28 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 25 to about 27 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 25 to about 26 bases in length.

[0102] In some embodiments, each single-stranded arm is each, individually, from about 25 to about 35 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 26 to about 35 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 27 to about 35 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 28 to about 35 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 29 to about 35 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 30 to about 35 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 31 to about 35 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 32 to about 35 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 33 to about 35 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 34 to about 35 bases in length.

[0103] In some embodiments, each single-stranded arm is each, individually, from about 12 to about 18 bases in length. In some embodiments, each single- stranded arm is each, individually, from about 13 to about 18 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 14 to about 18 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 15 to about 18 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 16 to about 18 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 17 to about 18 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 12 to about 17 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 12 to about 16 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 12 to about 15 bases in length. In some embodiments, each single-stranded arm is each, individually, from about 12 to about 14 bases in length. In some embodiments, each singlestranded arm is each, individually, from about 12 to about 13 bases in length.

[0104] In some embodiments, each single-stranded arm is each, individually, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 ,19 ,20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 125, 150, 175, 200, or more than 200 bases in length or any length in-between any of the recited values. In some embodiments, each single-stranded arm is each, individually, 4 bases in length. In some embodiments, each single-stranded arm is each, individually, 5 bases in length. In some embodiments, each single-stranded arm is each, individually, 6 bases in length. In some embodiments, each single-stranded arm is each, individually, 7 bases in length. In some embodiments, each single-stranded arm is each, individually, 8 bases in length. In some embodiments, each single-stranded arm is each, individually, 9 bases in length. In some embodiments, each single-stranded arm is each, individually, 10 bases in length. In some embodiments, each single-stranded arm is each, individually, 11 bases in length. In some embodiments, each single-stranded arm is each, individually, 12 bases in length. In some embodiments, each single- stranded arm is each, individually, 13 bases in length. In some embodiments, each single-stranded arm is each, individually, 14 bases in length. In some embodiments, each single-stranded arm is each, individually, 15 bases in length. In some embodiments, each single- stranded arm is each, individually, 16 bases in length. In some embodiments, each single-stranded arm is each, individually, 17 bases in length. In some embodiments, each single-stranded arm is each, individually, 18 bases in length. In some embodiments, each single-stranded arm is each, individually, 19 bases in length. In some embodiments, each single-stranded arm is each, individually, 20 bases in length. In some embodiments, each single-stranded arm is each, individually, 21 bases in length. In some embodiments, each single-stranded arm is each, individually, 22 bases in length. In some embodiments, each single-stranded arm is each, individually, 23 bases in length. In some embodiments, each single-stranded arm is each, individually, 24 bases in length. In some embodiments, each single- stranded arm is each, individually, 25 bases in length. In some embodiments, each single-stranded arm is each, individually, 26 bases in length. In some embodiments, each single-stranded arm is each, individually, 27 bases in length. In some embodiments, each single-stranded arm is each, individually, 28 bases in length. In some embodiments, each single-stranded arm is each, individually, 29 bases in length. In some embodiments, each single-stranded arm is each, individually, 30 bases in length. In some embodiments, each single-stranded arm is each, individually, 31 bases in length. In some embodiments, each single-stranded arm is each, individually, 32 bases in length. In some embodiments, each single-stranded arm is each, individually, 33 bases in length. In some embodiments, each single- stranded arm is each, individually, 34 bases in length. In some embodiments, each single-stranded arm is each, individually, 35 bases in length. In some embodiments, each single-stranded arm is each, individually, 36 bases in length. In some embodiments, each single-stranded arm is each, individually, 37 bases in length. In some embodiments, each single- stranded arm is each, individually, 38 bases in length. In some embodiments, each single-stranded arm is each, individually, 39 bases in length. In some embodiments, each single-stranded arm is each, individually, 40 bases in length. In some embodiments, each single-stranded arm is each, individually, 41 bases in length. In some embodiments, each single-stranded arm is each, individually, 42 bases in length. In some embodiments, each single-stranded arm is each, individually, 43 bases in length. In some embodiments, each single-stranded arm is each, individually, 44 bases in length. In some embodiments, each single-stranded arm is each, individually, 45 bases in length. In some embodiments, each single-stranded arm is each, individually, 46 bases in length. In some embodiments, each single- stranded arm is each, individually, 47 bases in length. In some embodiments, each single-stranded arm is each, individually, 48 bases in length. In some embodiments, each single-stranded arm is each, individually, 49 bases in length. In some embodiments, each single- stranded arm is each, individually, 50 bases in length. In some embodiments, each single-stranded arm is each, individually, 55 bases in length. In some embodiments, each single-stranded arm is each, individually, 60 bases in length. In some embodiments, each single-stranded arm is each, individually, 65 bases in length. In some embodiments, each single-stranded arm is each, individually, 70 bases in length. In some embodiments, each single-stranded arm is each, individually, 75 bases in length. In some embodiments, each single-stranded arm is each, individually, 80 bases in length. In some embodiments, each single-stranded arm is each, individually, 85 bases in length. In some embodiments, each single-stranded arm is each, individually, 90 bases in length. In some embodiments, each single- stranded arm is each, individually, 95 bases in length. In some embodiments, each single-stranded arm is each, individually, 100 bases in length. In some embodiments, each single-stranded arm is each, individually, 125 bases in length. In some embodiments, each single-stranded arm is each, individually, 150 bases in length. In some embodiments, each single-stranded arm is each, individually, 175 bases in length. In some embodiments, each single-stranded arm is each, individually, 200 bases in length. In some embodiments, each single-stranded arm is each, individually, more than 200 bases in length.

[0105] In some embodiments, the oligonucleotides may comprise one or two hinge segments joining any of the single-stranded arms to the double-stranded region. Each hinge segment may be from 1 to 4 nucleotides in length, from 2 to 4 nucleotides in length, 1 nucleotide in length, 2 nucleotides in length, 3 nucleotides in length, or 4 nucleotides in length. In some embodiments, the nucleotide sequence of the hinge segment 5' to the double-stranded region is CA, and the nucleotide sequence of the hinge segment 3' to the double-stranded region is AC. It is to be understood that the hinge segments are separate from the double- stranded portion and the single- stranded arm. For example, a first oligonucleotide may comprise a first single stranded arm of 50 bases in length, a complementary portion of 35 bases in length, and a second single stranded arm of 50 bases in length, thus comprising a first oligonucleotide of 135 bases in length. Alternatively, the first oligonucleotide may comprise a first single stranded arm of 50 bases in length, a first hinge segment of 4 bases in length, a complementary portion of 35 bases in length, a second hinge segment of 4 bases in length, and a second single stranded arm of 50 bases in length, thus comprising a first oligonucleotide of 143 bases in length. These examples are exemplary only to demonstrate how the length of the oligonucleotide may be determined and are not meant to be construed as limiting in any way. Each of the single- stranded arms has a nucleic acid sequence that can be the same as or different from any other single-stranded arm. In some embodiments, the nucleotide sequence of each of the four single- stranded arms is identical. In some embodiments, the nucleotide sequences of three of the four single-stranded arms are identical to each other and different than the nucleotide sequence of the fourth single- stranded arm. In some embodiments, the nucleotide sequences of two of the four single-stranded arms are identical to each other and different than the nucleotide sequences of the other two single-stranded arms. In some embodiments, the nucleotide sequences of two of the four single-stranded arms are identical to each other and the nucleotide sequences of the other two of the four singlestranded arms are identical to each other, wherein the nucleotide sequence of the first two single- stranded arms is different than the nucleotide sequences of the second two singlestranded arms. In some embodiments, the nucleotide sequence of each of the four singlestranded arms is different. Thus, the nucleotide sequence of any particular single- stranded arm provides flexibility in design choice and can be used to specifically bind to or be conjugated to a particular linking oligonucleotide (which may or may not be further conjugated to a targeting agent or a cargo molecule as provided for herein) or to another single- stranded arm of another monomeric nucleic acid carrier. In some embodiments, one or more of the single stranded arms is complementary to a linking oligonucleotide that is conjugated to a targeting agent. In some embodiments, one or more of the single stranded arms is complementary to a DNA dendrimer binding sequence (DBS) as provided for herein. In some embodiments, one or more of the single stranded arms is complementary to a linking oligonucleotide that is conjugated to a targeting agent and one or more of the single stranded arms is complementary to a DNA dendrimer binding sequence (DBS) as provided for herein. Any two nucleic sequences having a degree of complementarity may be used to attach a single stranded arm of the DNA dendrimer to a linking oligonucleotide or a DBS, wherein the two nucleic acid strands comprise the DBS and the corresponding single stranded arm. The skilled artisan would readily recognize which nucleic acid base pairs are complementary and which are not and thus be able to envisage two nucleic acid sequences having a desired degree of complementarity. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 30% to 100% complementary, from 35% to 100% complementary, from 40% to 100% complementary, from 45% to 100% complementary, from 50% to 100% complementary, from 55% to 100% complementary, from 60% to 100% complementary, from 65% to 100% complementary, from 70% to 100% complementary, from 75% to 100% complementary, from 80% to 100% complementary, from 85% to 100% complementary, from 90% to 100% complementary, from 95% to 100% complementary, or any value or range in-between. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 30% to 95% complementary, from 30% to 90% complementary, from 30% to 85% complementary, from 30% to 80% complementary, from 30% to 75% complementary, from 30% to 70% complementary, from 30% to 65% complementary, from 30% to 60% complementary, from 30% to 55% complementary, from 30% to 50% complementary, from 30% to 45% complementary, from 30% to 40% complementary, from 30% to 35% complementary, or any value or range in-between.

[0106] In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are less than 30% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 30%, 35%, 40%, 45%, 50%, 55%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 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% complementary, or any value or range inbetween. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 30% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 35% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 40% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 45% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 50% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 55% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 60% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 61% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 62% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 63% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 64% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 65% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 66% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 67% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 68% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 69% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 70% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 71% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 72% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 73% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 74% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 75% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 76% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 77% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 78% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 79% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 80% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 81% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 82% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 83% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 84% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 85% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 86% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 87% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 88% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 89% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 90% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 91% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 92% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 93% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 94% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 95% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 96% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 97% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 98% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 99% complementary. In some embodiments, the two nucleic acid sequences (e.g. the single stranded arm and the linking oligonucleotide or the single stranded arm and the DBS) comprise sequences which are 100% complementary.

[0107] DNA dendrimers are commercially available. In addition, the structural design and assembly of DNA dendrimers is generally known in the art. See, for instance, U.S. Pat. Nos. 5,175,270 and 6,274,723, each of which are incorporated herein by reference in their entireties. An initiating monomer constitutes the approximate center of a dendrimer, depending on the type of branching in the dendrimer. The three-dimensional assembly of extending monomers around the initiating monomer forms the interior volume of the dendrimer. The last, outer layer of extending monomers forms the surface of the dendrimer. Thus, the assembly of a dendrimer results in a three-dimensional shape, typically, but not exclusively, a roughly spherical shape comprising layers of extending monomers. The outer layer comprises numerous binding sites.

[0108] More specifically, DNA dendrimers may be prepared by protocols having the following features, (i) The starting material is a double-stranded duplex of DNA (i.e. the double-stranded region) with 5' and 3' single-stranded overhangs, or “binding arms,” attached to the duplex trunk (e.g., four binding arms total), called the “initiating monomer,” which is descriptive of its role in the assembly of a dendrimer. Each initiating monomer's 5' and 3' binding arms are annealed to complementary binding arms on “extending monomers” that have similar composition and morphology, (ii) A subset of the four binding arms on each extending monomer is complementary to the binding arms on the initiating monomer. The non-complementary binding arms of the extending monomers are inactive for annealing to the initiating monomer. Typically, four extending monomers can anneal to the initiating monomer to yield a single-layer, or one-layer, dendrimer in solution, (iii) To add another layer of extending monomers to dendrimers, one typically adds similar but distinguishable extending monomers, in which each monomer has a subset of its four binding arms that is complementary to binding arms on the dendrimer. Thus, a one-layer dendrimer can be converted to a two-layer dendrimer, and so on, stepwise, until a desired size of dendrimer is reached. The table below provides details of the structural elements of varying dendrimer preparations. These are exemplary only and are not meant to be limiting in any way.

[0109] After assembly, a DNA dendrimer can be crosslinked to maintain and stabilize the structure of the dendrimer. Crosslinking hybridized regions between monomers (i.e., intermonomer crosslinking) or between monomers and the nucleic acids that carry detectable labels, as well as between trunk portions (intra-monomer crosslinking), can stabilize the structure of the polynucleotide dendrimer. Similarly, any hybridized region of any DNA- based carrier may be crosslinked to stabilize the carrier. Individual units of carrier may also be crosslinked into a polymolecular carrier. Such crosslinking chemistries are well known in the art. See, e.g., Cimino et al., Annu. Rev. Biochem. 54: 1151-1193 (1985); Shi et al., Biochemistry 25:5895-5902 (1986); and Cimino et al., Biochemistry 25:3013-3020 (1986). See also U.S. Pat. No. 4,196,281. Non-limiting examples of suitable crosslinking agents include: psoralens (including but not limited to 8-methoxypsoralen and angelicin), mitomycin C, daunomycin, ethidium diazide, cisplatin, transplatin, carboplatin, 8-methoxypsoralen, mechlorethamine, oxaliplatin, and carbodiimide compounds, among others.

[0110] The polynucleotide strands used in the monomers of dendrimers or in the other DNA- based carriers, can be made using standard techniques for synthesis of nucleic acids. These techniques can be biological or chemical. The techniques and procedures are generally performed according to conventional methods in the art and in various general references (e.g., Sambrook et al., 2001, supra; Ausubel et al., eds., 2005, supra, and Gerhardt et al., eds., 1994, Methods for General and Molecular Bacteriology, American Society for Microbiology, Washington, D.C.).

[0111] In some embodiments, polynucleotides are chemically synthesized using methods known in the art. See, e.g., Gait, 1985, Oligonucleotide Synthesis: A Practical Approach (IRL Press, Oxford, England. In another embodiment, polynucleotides are synthesized enzymatically using the polymerase chain reaction (PCR). One PCR method suitable for generating single- stranded polynucleotides is multi-cycle PCR using a single primer, which thereby amplifies a single strand. Nucleic acids may be purified by any suitable means, as are well known in the art, prior to their use. For example, the nucleic acids can be purified by reverse phase or ion exchange HPLC, size exclusion chromatography or gel electrophoresis. The skilled artisan will recognize that the method of purification will depend in part on the size of the nucleic acid to be purified.

[0112] The outer layer of a DNA dendrimer can have at least two types of binding arms. These binding arms can be used for attaching one or more types of moieties. In some embodiments, the DNA dendrimer of the compositions can bind or attach to targeting moieties, cargoes, support molecules, and the like.

[0113] In some embodiments, the DNA-based carrier is associated with a secondary carrier, which may serve as a scaffold for the DNA-based carriers. Examples of such secondary carriers include, but are not limited to, liposomes, non-DNA dendrimers, polymer carriers, microbubbles, paramagnetic and ferromagnetic particles, self-assembled polymers, polymersomes, filomicelles, albumin particles, lipoproteins, and the like. A self- assembled polymer is one that is formed by self-assembly of monomolecular building blocks. These building blocks can be amphiphilic copolymers, which comprise a hydrophilic component (such as, but not limited to, polyethylenimine or polyethyleneglycol) and a hydrophobic component (such a, but not limited to, aliphatic polyesters) into a core-shell-type structure. These structures that are not maintained by direct conjugation or crosslink of the building blocks are known to as micelles and can vary in their morphology, for instance from spherical micelles (“polymersomes”) to elongated or filamentous rods (“filomicelles”). The sizes of these structures may also vary from the nanometer to the micrometer size range. Once formed by self-assembly, these structures may alternatively be further crosslinked chemically to increase their stability. Hydrophobic cargoes can be embedded into the hydrophobic regions of the carrier, while hydrophilic cargoes can be incorporated into an internal aqueous core or to the external hydrophilic corona.

[0114] In some embodiments, the DNA-based carrier is linked to the surface of the secondary carrier. In some embodiments, the DNA-based carrier is not linked but is associated with the secondary carrier by virtue of being in the same composition. In some embodiments, the cargos and targeting moieties can be linked to the DNA-based carrier, or to the scaffold carrier, using methods described herein and known in the art.

[0115] B. Targeting Moieties

[0116] In some embodiments, the DNA-based carrier is directed to a specific cell by linking a targeting moiety to the carrier, to a secondary carrier and / or a cargo. In some embodiments, the targeting moiety is linked to the DNA-based carrier. In some embodiments, the targeting moiety is linked to a secondary carrier. A targeting moiety may be an antibody, a naturally- occurring ligand for the receptor or a functional derivative thereof, a vitamin, a hormone, a small molecule mimetic of a naturally-occurring ligand, a peptide, a polypeptide, a peptidomimetic, a carbohydrate, a lipid, a FN3 domain, an aptamer, a nucleic acid, a toxin, a component of a microorganism, or any other molecule provided it binds specifically to the cell surface molecule and induces endocytosis of the bound moiety.

[0117] Without being bound to any particular theory, the targeting moiety can bind specifically to a molecule on the cell surface of a target cell. The targeting moiety can be bind to a cell surface molecule, which can, in some embodiments, induce endocytosis of the DNA- based carrier. Non-limiting examples of cell surface molecule that may be targeted include cell surface proteins, carbohydrates, and lipids. Cell surface molecules that may be targeted include molecules associated with classical endocytosis and those associated with non- classical endocytosis. In some embodiments, the target cell surface molecule is a cell adhesion molecule (CAM). Cell adhesion molecules useful in the invention include, but are not limited to, neural specific adhesion molecules (e.g., NCAM) and systemic intercellular adhesion molecules. Systemic CAMs include intercellular adhesion molecules (e.g., ICAM-1, ICAM-2, ICAM-3), platelet-endothelial cell adhesion molecule (PECAM), activated leukocyte cell adhesion molecule (ALCAM), B-lymphocyte cell adhesion molecule (BL-CAM), vascular cell adhesion molecule (VCAM), mucosal vascular addressin cell adhesion molecule (MAdCAM), CD44, LFA-2 (CD2), LFA-3 (CD58), basigin (CD147) and the like. In some embodiments, the cell surface molecule is CD71.

[0118] In some embodiments, the targeting moiety is an antibody that specifically binds to a target cell surface molecule. In some embodiments, the antibody is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a humanized antibody, a synthetic antibody, a heavy chain antibody, and a biologically active fragment of an antibody, wherein the biologically active fragment is a Fab fragment, a F(ab')2 fragment, an sc-Fv fragment.

[0119] When the antibody used as a targeting moiety in the compositions and methods of the invention is a polyclonal antibody (IgG), the antibody is generated by inoculating a suitable animal with the targeted cell surface molecule. Antibodies produced in the inoculated animal which specifically bind to the cell surface molecule are then isolated from fluid obtained from the animal. Antibodies may be generated in this manner in several non-human mammals such as, but not limited to goat, sheep, horse, camel, rabbit, and donkey. Methods for generating polyclonal antibodies are well known in the art and are described, for example in Harlow, et al. (1988, In: Antibodies, A Laboratory Manual, Cold Spring Harbor, N.Y.).

[0120] Monoclonal antibodies directed against a full-length targeted cell surface molecule or fragments thereof may be prepared using any well-known monoclonal antibody preparation procedures, such as those described, for example, in Harlow et al. (1988, In: Antibodies, A Laboratory Manual, Cold Spring Harbor, N.Y.) and in Tuszynski et al. (1988, Blood, 72:109- 115). Human monoclonal antibodies may be prepared by the method described in U.S. patent publication 2003 / 0224490. Monoclonal antibodies directed against an antigen are generated from mice immunized with the antigen using standard procedures as referenced herein. Nucleic acid encoding the monoclonal antibody obtained using the procedures described herein may be cloned and sequenced using technology available in the art, and is described, for example, in Wright et al. (1992, Critical Rev. in Immunol. 12(3,4): 125-168) and the references cited therein. To prepare a targeted DNA-based carrier, such as a DNA dendrimer, the targeting moiety can be linked to the DNA-based carrier, or a secondary carrier or a cargo that is linked to, or associated with, a composition comprising the DNA-based carrier. A single targeting moiety may be linked to the DNA-based carrier or secondary carrier. Alternatively, a plurality of (e.g., two or more) targeting moieties are linked to the DNA-based carrier, secondary carrier or cargo. When a plurality of targeting moieties are linked to a carrier or cargo, the moieties may target the same cell surface molecule or may target different cell surface molecules. If targeting different cell surface molecules, these molecules may be associated with the same endocytic pathway or different endocytic pathways. The targeting moiety may also not be associated with an endocytic pathway. If targeting different cell surface molecules, the cell surface molecules may be present on the same cell type or may be present on different cell types.

[0121] Linking may be non-covalent or covalent. A targeting moiety may be linked directly to one or more of the polynucleotide strands comprising the DNA-based carrier. Alternatively, a targeting moiety is linked to a linker molecule which is in turn linked to the DNA-based carrier. In some embodiments, wherein the DNA-based carrier is a DNA dendrimer, the linker molecule is an oligonucleotide comprising a sequence substantially complementary to a sequence present in one of the binding arms on the surface of the DNA dendrimer. Thus, the targeting moiety is linked indirectly and non-covalently to the DNA dendrimer by hybridization of the oligonucleotide to a binding arm. This approach is also applicable to other DNA-based carriers. Optionally, the hybridized oligonucleotide is also cross-linked to the DNA dendrimer. Cross-linking chemistries are disclosed elsewhere herein. When not cross-linked, hybridization between the DNA dendrimer and an oligonucleotide linked to a targeting moiety should be sufficiently long-lived under the conditions of use. Determination of binding free energies for nucleic acid molecules is well known in the art (see, e.g., Turner et al., 1987, CSH Symp. Quant. Biol. LII pp. 123-133; Freier et al., 1986, Proc. Nat. Acad. Sci. USA 83:9373-9377; Turner et al., 1987, J. Am. Chern. Soc. 109:3783- 3785; Chavali et al., 2005, Bioinformatics 21(20):3918-3925).

[0122] In some embodiments, the linker is a secondary IgG Fc-specific antibody which is linked to the DNA-based carrier. In some embodiments, the antibody specifically binds to the Fc portion of the primary IgG antibody, e.g., the targeting moiety or an intervening antibody. The secondary antibody is preferably specific for the species source of the primary antibody. For instance, if the targeting moiety is a human IgG antibody, the secondary antibody is antihuman IgG. In another aspect, the secondary antibody recognizes epitopes of the entire primary antibody, not just the Fc portion. Alternatively, the linker is an Fc gamma receptor that binds specifically to the Fc portion of an IgG antibody. In any of these, the carrier may be readily linked to any targeting moiety that is an IgG antibody.

[0123] Non-covalent linkages include, but are not limited to, affinity binding pairs, such as biotin-streptavidin and immunoaffinity, having sufficiently high affinity to maintain the linkage during use and are well-known in the art. The art is also replete with conjugation chemistries useful for covalently linking a target moiety to a DNA-based carrier, secondary carrier or cargo, directly or via a linker. Art-recognized covalent coupling techniques are disclosed, for instance, in U.S. Pat. Nos. 5,416,016, 6,335,435, 6,528,631, 6,861,514 and 6,919,439, incorporated herein by reference in their entirety. Other conjugation chemistries are disclosed in U.S. Patent Publication No. 20040249178, incorporated herein by reference in its entirety. Still other conjugation chemistries include: p-hydroxy-benzoic acid linkers (Chang-Po et al., 2002, Bioconjugate Chem. 13(3):525-529) ; native ligation (Stetsenko et al., 2000, J Org. Chem. 65:4900-4908): disulfide bridge conjugates (Oehlke et al., 2002, Eur J. Biochem. 269:4025-4032 and Rogers et al., 2004, Nuc Acids Res. 32(22) 6595-6604); maleimide linkers (Zhu et al., 1993, Antisense Res Dev. 3:265-275); thioester linkers (Ede et al., 1994, Bioconjug Chem. 5:373-378); Diels-Alder cycloaddition (Marchan et al., 2006. Nuc Acids Res. 34(3): e24, 2006 Feb. 14 Epub); U.S. Pat. No. 6,656,730 and the like. For reviews of peptide-oligonucleotide conjugation chemistries, see also Tung et al., 2000, Bioconjugate Chem. 11:605-618; Zatsepin et al., 2005, Curr Pharm Des. 11(28):3639-3654; and luliano, 2005, Curr Opin Mol. Ther. 7(2): 132-136.

[0124] C. Cargos

[0125] The compositions provided herein can also comprise a cargo. In some embodiments, the cargo is attached directly or indirectly to a DNA dendrimer. A cargo that is attached to the DNA dendrimer is associated with the DNA dendrimer via a linker or other type of molecule (adaptor), and the like. One, two, or more different cargoes may be delivered by a targeted DNA-based carrier. Cargoes that can be delivered in accordance the compositions disclosed herein include, but are not limited to, a variety of agents, including, but not limited to, therapeutic agents, imaging agents, monitoring agents, chemotherapeutic agents, anti- oncogenic agents, anti- angiogenic agents, tumor suppressor agents, anti-microbial agents, enzyme replacement agents, gene expression modulating agents and expression constructs comprising a nucleic acid encoding a therapeutic protein or nucleic acid. In some embodiments, cargo may be an exogenous material or an endogenous material. Cargoes include any molecule that induces an effect in a cell, including any protein, nucleic acid, small molecule, carbohydrate, or lipid. Cargoes may be peptides, proteins (including enzymes, antibodies and peptidic hormones), ligands of cytoskeleton, nucleic acid, small molecules, non-peptidic hormones and the like. Nucleic acids and cargo polynucleotides that may be delivered by the method of the invention include synthetic and natural nucleic acid material, including DNA, RNA, transposon DNA, antisense nucleic acids, dsRNA, siRNAs, transcription RNA, messenger RNA, ribosomal RNA, small nucleolar RNA, microRNA, ribozymes, plasmids, and expression constructs. When the cargo is or comprises a nucleic acid, the nucleic acid may be a separate entity from the DNA-based carrier. In these embodiments, the DNA-based carrier is not itself the cargo.

[0126] In some embodiments, the cargo is a polynucleotide comprising at least one promoter and at least one coding sequence that encodes for at least one molecule of interest. For example, the cargo polynucleotide may comprise one promoter and two or more coding sequences that encode for different molecules of interest, or one promoter for each coding sequence present. In some embodiments, the promoter or promoters are tissue specific promoters that transcript or translate the at least one molecule of interest only when the composition comprising the cargo polynucleotide is present within a target cell that matches the tissue specific promoter. Tissue specific promoters are known in the art and any such tissue specific promoter is within the scope of the present disclosure.

[0127] In some embodiments, the molecule of interest is a gene product, such as an enzyme, protein, receptor, and the like. In some embodiments, the cargo polynucleotide encodes two or more molecules of interest. In some embodiments, at least one of the molecules of interest is a detectable molecule, such as, but not limited to, proteins are tagged, detectable via bioluminescence, fluorescence, radiation signals, or some combination thereof. In some embodiments, such molecules of interest are useful for biodistribution studies and other quantitative and / or real-time assessments.

[0128] In some embodiments, the cargo polynucleotide may have one or more structures or topologies. For example, the cargo polynucleotide may exist as a fully circular, double stranded DNA or RNA with no free 5’ or 3’ ends. In some embodiments, the cargo polynucleotide is a plasmid. In some embodiments, the cargo polynucleotide can be a nicked circular polynucleotide, a linear polynucleotide with a closed 5’ and 3’ end, a linear polynucleotide with open 5’ and 3’ ends, and a linear polynucleotide with one open and one closed end. In some embodiments, a nicked circular polynucleotide is a fully circular, double stranded DNA or RNA that has at least one break in a single strand of the DNA or RNA. As used herein, a nicked circular polynucleotide is understood to be a circular polynucleotide that has a 1-100 base gap as compared to the un- nicked polynucleotide. In some embodiments, the nick results in a 1-100 base gap, a 2-100 base gap, a 3-100 base gap, a 4- 100 base gap, a 5-100 base gap, a 6-100 base gap, a 7-100 base gap, an 8-100 base gap, a 9- 100 base gap, a 10-100 base gap, a 15-100 base gap, a 20-100 base gap, a 25-100 base gap, a 30-100 base gap, a 35-100 base gap, a 40-100 base gap, a 45-100 base gap, a 50-100 base gap, a 60-100 base gap, a 70-100 base gap, an 80-100 base gap, a 90-100 base gap, or a base gap having any value or range in-between. In some embodiments, the nick results in a 1-90 base gap, a 1-80 base gap, a 1-70 base gap, a 1-60 base gap, a 1-50 base gap, a 1-45 base gap, a 1-40 base gap, a 1-35 base gap, a 1-30 base gap, a 1-25 base gap, a 1-20 base gap, a 1-15 base gap, a 1-10 base gap, a 1-9 base gap, a 1-8 base gap, a 1-7 base gap, a 1-6 base gap, a 1- 5 base gap, a 1-4 base gap, a 1-3 base gap, a 1-2 base gap, or any value or range in-between. In some embodiments, the nick can be due to the action of a nicking restriction enzyme. In some embodiments, a linear polynucleotide has defined 5’ and 3’ ends, with either end, or both, being optionally closed via a covalent bond.

[0129] The different topologies or structures can be used for different attachments to the DNA dendrimer.

[0130] Provided herein is a plasmid comprising a plasmid backbone comprising at least two restriction sites, at least one promoter, and at least one coding sequence encoding for at least one molecule of interest, wherein the plasmid can form a cargo polynucleotide with various topologies, such as those provided for herein. For example, a gene cassette comprising a promoter sequence and a coding sequence encoding for at least one molecule of interest can be inserted into the plasmid backbone. The resulting plasmid can have a fully circular topology, and if such a topology is desired, no further steps are required. However, if a different topology is desired, the plasmid can be contacted with one or more restriction enzymes to break one or both nucleotide strands of the plasmid and create a nicked circular polynucleotide, a linear polynucleotide with a closed 5’ and 3’ end, a linear polynucleotide with open 5’ and 3’ ends, or a linear polynucleotide with one open and one closed end. In some embodiments, closed ends on liner polynucleotides are formed using TelN Protelomerase.

[0131] In some embodiments, a cargo polynucleotide is transported to a nucleus of a cell. In some embodiments, a cargo polynucleotide comprises one or more of a DNA targeting sequence (DTS) or a nuclear localization signal (NLS). DTS and NLS are, independently, short amino acid sequences that target proteins and associated nucleic acids for import into the nucleus. In a non- limiting example, an NLS that can be encoded by the cargo polynucleotide has the amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to YPDEVKRKKKP (SEQ ID NO: 1), SLLESPFDKPDEVKRKKKPPTSHQSDATAEDDSSSKKK (SEQ ID NO: 2), PKKKRKV (SEQ ID NO: 15), or KKPNKKKRKE (SEQ ID NO: 46). These are non-limiting examples of NLS sequences and any NLS can be used. In some embodiments, the NLS comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 1. In some embodiments, the NLS comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 2. In some embodiments, the NLS comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 15. In some embodiments, the NLS comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 46. In some embodiments, the NLS comprises an amino acid sequence of any one of SEQ ID NO: 1, 2, 15, or 46. In some embodiments, the NLS comprises an amino acid sequence of SEQ ID NO: 1. In some embodiments, the NLS comprises an amino acid sequence of SEQ ID NO: 2. In some embodiments, the NLS comprises an amino acid sequence of SEQ ID NO: 15. In some embodiments, the NLS comprises an amino acid sequence of SEQ ID NO: 46. In some embodiments, at least one DTS, at least one NLS, or both can be located anywhere within or in respect to the cargo polynucleotide. For example, the DTS, NLS, or both can be located upstream or downstream of the at least one promoter of the cargo polynucleotide. In such a molecule, the polypeptide is linked to the cargo polynucleotide.

[0132] In some embodiments, one or more DTS or NLS sequences can be attached or linked to the cargo polynucleotide, instead of being located within the cargo polynucleotide. In some embodiments, the one or more DTS or NLS sequences can be included in any adaptor molecule described herein, wherein the adaptor molecule is linked to the cargo polynucleotide. In some embodiments, the one or more DTS or NLS sequences can be linked directly to the cargo polynucleotide without being associated with a corresponding adaptor molecule. In some embodiments, the DTS or NLS sequence can be attached to a cargo polynucleotide via a modified nucleotide. For example, a DTS or NLS sequence can be attached to a nicked circular cargo polynucleotide at the nick site, optionally where a modified nucleotide has been first inserted at the nick site.

[0133] In some embodiments, the cargo, including cargo polynucleotides described herein, can be linked to a DNA dendrimer directly by any covalent or non-covalent interaction or bond described herein, such as a hydrogen bond. Thus, in some embodiments, the cargo polynucleotide comprises a DNA dendrimer binding sequence (DBS), which links the cargo polynucleotide to the DNA dendrimer. In some embodiments, the DBS comprises a nucleic acid sequence that is complimentary to a nucleic acid sequence on the DNA dendrimer. In a non-limiting example, the DBS comprises a nucleic acid sequence that is complimentary to at least one binding arm of the DNA dendrimer. In some embodiments, the DBS binds to the DNA dendrimer via hydrogen bonding.

[0134] In some embodiments, the DBS comprises a nucleic acid sequence selected from any one of: TAGAGGTAACAACTAGCGTACAA (SEQ ID NO: 3);

[0135] TAGAGGTAACAACTAGCGTACAATTTTTTTTTT (SEQ ID NO: 4);

[0136] TCAGCTTGTACTCTAGTTGTTACCTCTAATGCTGGACC (SEQ ID NO: 10); GCACCCTACAGAGTAACCTAGATTGATCAAACACCTCA (SEQ ID NO: 11); CCTCAGCTTGTACTCTAGTTGTTACCTCTAATGCTGGACCTCAGC (SEQ ID NO: 22); or CCTCAGCACCCTACAGAGTAACCTAGATTGATCAAACACCTCAGC (SEQ ID NO: 23). In some embodiments, the DBS comprises a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 3, 4, 22, or 23. In some embodiments, the DBS comprises a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 3. In some embodiments, the DBS comprises a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 4. In some embodiments, the DBS comprises a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10. In some embodiments, the DBS comprises a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 11. In some embodiments, the DBS comprises a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 22. In some embodiments, the DBS comprises a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 23. In some embodiments, the DBS comprises a nucleic acid sequence of any one of SEQ ID NOs: 3, 4, 22, or 23. In some embodiments, the DBS comprises a nucleic acid sequence of SEQ ID NO: 3. In some embodiments, the DBS comprises a nucleic acid sequence of SEQ ID NO: 4. In some embodiments, the DBS comprises a nucleic acid sequence of SEQ ID NO: 10. In some embodiments, the DBS comprises a nucleic acid sequence of SEQ ID NO: 11. In some embodiments, the DBS comprises a nucleic acid sequence of SEQ ID NO: 22. In some embodiments, the DBS comprises a nucleic acid sequence of SEQ ID NO: 23.

[0137] In some embodiments, the DBS comprises a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10, provided that the nucleic acid sequence comprises at least 20 contiguous nucleic acids of the sequence of SEQ ID NO: 10. The at least 20 contiguous nucleic acids of SEQ ID NO: 10 may be any 20 contiguous nucleic acids. Thus, the at least 20 contiguous nucleic acids may comprise nucleic acids 1-20 of SEQ ID NO: 10, nucleic acids 2-21 of SEQ ID NO: 10, nucleic acids 3-22 of SEQ ID NO: 10, nucleic acids 4-23 of SEQ ID NO: 10, nucleic acids 5- 24 of SEQ ID NO: 10, nucleic acids 6-25 of SEQ ID NO: 10, nucleic acids 7-26 of SEQ ID NO: 10, nucleic acids 8-27 of SEQ ID NO: 10, nucleic acids 9-28 of SEQ ID NO: 10, nucleic acids 10-29 of SEQ ID NO: 10, nucleic acids 11-30 of SEQ ID NO: 10, or nucleic acids 12- 31 of SEQ ID NO: 10. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 1-20 of SEQ ID NO: 10. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 2-21 of SEQ ID NO: 10. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 3-22 of SEQ ID NO: 10. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 4-23 of SEQ ID NO: 10. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 5-24 of SEQ ID NO: 10. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 6-25 of SEQ ID NO: 10. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 7-26 of SEQ ID NO: 10. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 8-27 of SEQ ID NO: 10. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 9-28 of SEQ ID NO: 10. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 10-29 of SEQ ID NO: 10. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 11-30 of SEQ ID NO: 10. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 12-31 of SEQ ID NO: 10.

[0138] In some non-limiting embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10, wherein the nucleic acid sequence comprises at least 20 contiguous nucleic acids of the sequence of SEQ ID NO: 10, comprises 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31 contiguous nucleic acids of the sequence of SEQ ID NO: 10. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10, comprises at least 20 contiguous nucleic acids of the sequence of SEQ ID NO: 10. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10, comprises at least 21 contiguous nucleic acids of the sequence of SEQ ID NO: 10. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10, comprises at least 22 contiguous nucleic acids of the sequence of SEQ ID NO: 10. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10, comprises at least 23 contiguous nucleic acids of the sequence of SEQ ID NO: 10. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10, comprises at least 24 contiguous nucleic acids of the sequence of SEQ ID NO: 10. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10, comprises at least 25 contiguous nucleic acids of the sequence of SEQ ID NO: 10. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10, comprises at least 26 contiguous nucleic acids of the sequence of SEQ ID NO: 10. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10, comprises at least 27 contiguous nucleic acids of the sequence of SEQ ID NO: 10. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10, comprises at least 28 contiguous nucleic acids of the sequence of SEQ ID NO: 10. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10, comprises at least 29 contiguous nucleic acids of the sequence of SEQ ID NO: 10. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10, comprises at least 30 contiguous nucleic acids of the sequence of SEQ ID NO: 10. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 10, comprises at least 31 contiguous nucleic acids of the sequence of SEQ ID NO: 10.

[0139] In some embodiments, the DBS comprises a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 11, provided that the nucleic acid sequence comprises at least 20 contiguous nucleic acids of the sequence of SEQ ID NO: 11. The at least 20 contiguous nucleic acids of SEQ ID NO: 11 may be any 20 contiguous nucleic acids. Thus, the at least 20 contiguous nucleic acids may comprise nucleic acids 1-20 of SEQ ID NO: 11, nucleic acids 2-21 of SEQ ID NO: 11, nucleic acids 3-22 of SEQ ID NO: 1 1, nucleic acids 4-23 of SEQ ID NO: 11, nucleic acids 5- 24 of SEQ ID NO: 11, nucleic acids 6-25 of SEQ ID NO: 11, nucleic acids 7-26 of SEQ ID NO: 11, nucleic acids 8-27 of SEQ ID NO: 11, nucleic acids 9-28 of SEQ ID NO: 11, nucleic acids 10-29 of SEQ ID NO: 11, nucleic acids 11-30 of SEQ ID NO: 11, or nucleic acids 12- 31 of SEQ ID NO: 11. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 1-20 of SEQ ID NO: 11. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 2-21 of SEQ ID NO: 11. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 3-22 of SEQ ID NO: 11. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 4-23 of SEQ ID NO: 11. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 5-24 of SEQ ID NO: 11. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 6-25 of SEQ ID NO: 11. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 7-26 of SEQ ID NO: 11. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 8-27 of SEQ ID NO: 11. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 9-28 of SEQ ID NO: 11. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 10-29 of SEQ ID NO: 11. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 11-30 of SEQ ID NO: 11. In some embodiments, the at least 20 contiguous nucleic acids comprises nucleic acids 12-31 of SEQ ID NO: 11.

[0140] In some non-limiting embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 11, wherein the nucleic acid sequence comprises at least 20 contiguous nucleic acids of the sequence of SEQ ID NO: 11, comprises 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31 contiguous nucleic acids of the sequence of SEQ ID NO: 11. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 1 1 , comprises at least 20 contiguous nucleic acids of the sequence of SEQ ID NO: 11. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 11, comprises at least 21 contiguous nucleic acids of the sequence of SEQ ID NO: 11. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 11, comprises at least 22 contiguous nucleic acids of the sequence of SEQ ID NO: 11. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 11, comprises at least 23 contiguous nucleic acids of the sequence of SEQ ID NO: 11. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 11, comprises at least 24 contiguous nucleic acids of the sequence of SEQ ID NO: 11. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 11, comprises at least 25 contiguous nucleic acids of the sequence of SEQ ID NO: 11. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 11, comprises at least 26 contiguous nucleic acids of the sequence of SEQ ID NO: 11. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 1 1 , comprises at least 27 contiguous nucleic acids of the sequence of SEQ ID NO: 11. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 11, comprises at least 28 contiguous nucleic acids of the sequence of SEQ ID NO: 11. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 11 , comprises at least 29 contiguous nucleic acids of the sequence of SEQ ID NO: 11. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 11, comprises at least 30 contiguous nucleic acids of the sequence of SEQ ID NO: 11. In some embodiments, the DBS comprising a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 11, comprises at least 31 contiguous nucleic acids of the sequence of SEQ ID NO: 11.

[0141] In some embodiments, the DBS sequence further comprises a polythymine sequence at either the 5’ or 3’ end of the DBS sequence. These are non- limiting examples of DBS molecules and any DBS sequence can be used that is complimentary to the dendrimer arm. In some embodiments, the DBS and the dendrimer arm have a percent complementarity as provided for herein.

[0142] D. Adaptor Molecules

[0143] The cargo can also be linked to a DNA dendrimer by an adaptor molecule as provided for herein. In some embodiments, the adaptor molecule comprises a DBS sequence that links the adaptor molecule to the DNA dendrimer, and a cargo binding region that links to the cargo, for example, a cargo polynucleotide as provided for herein.

[0144] In some embodiments, the DBS comprises a nucleic acid sequence that is complimentary to a nucleic acid sequence on the DNA dendrimer. For example, the DBS comprises a nucleic acid sequence that is complimentary to at least one binding arm of the DNA dendrimer. In some embodiments, the DBS binds to the DNA dendrimer via hydrogen bonding. In some embodiments, the DBS comprises any DBS sequence disclosed herein. In some embodiments, any DBS sequence can be used that is complimentary to the dendrimer arm.

[0145] In some embodiments, the cargo binding region can be linked to the cargo polynucleotide by range of linkers known in the art. For example, the cargo binding region can comprise a nucleic acid sequence that is complimentary to at least one part of a cargo polynucleotide, and / or links to the cargo by DNA ligation. In another example, the cargo binding region can link to a cargo polynucleotide by chemical coupling, such as, but not limited to, click chemistry or EDC cross-linking. In some embodiments, the cargo binding region comprises at least one nucleotide with an amine, azide, or other reactive group. In some embodiments, the cargo binding region comprises at least one cysteine residue. The adaptor molecule can also have other regions or features included. In some embodiments, such regions or features can be located between the DBS and the cargo binding region but may also be located in any order within the adaptor molecule.

[0146] In some embodiments, the adaptor molecule further comprises at least one purification region. In some embodiments, purification region comprises at least one purification or affinity tag. The purification or affinity tag can be any such chemical or amino acid tag known in the art, for example, a polyhistidine tag such as, but not limited to, His6, His 12, and the like.

[0147] In some embodiments, the adaptor molecule further comprises a DTS, NLS, or both as provided for herein. In some embodiments, the DTS and NLS regions are located between the DBS and the cargo binding region. In some embodiments, the NLS comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 1, 2, 15, or 46. In some embodiments, the NLS comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 1. In some embodiments, the NLS comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 2. In some embodiments, the NLS comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 15. In some embodiments, the NLS comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 46. In some embodiments the NLS comprises an amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 15, or SEQ ID NO: 46. In some embodiments the NLS comprises an amino acid sequence of SEQ ID NO: 1. In some embodiments the NLS has an amino acid sequence of SEQ ID NO: 2. In some embodiments the NLS has an amino acid sequence of SEQ ID NO: 15. In some embodiments the NLS has an amino acid sequence of SEQ ID NO: 46.

[0148] In some embodiments, the DTS comprises any sequence that promotes an interaction with DNA. For example, a DTS sequence may comprise a transcription factor binding sequence or the like. Such sequences are known in the art and are within the scope of the present disclosure. Alternatively, the skilled artisan may utilize a DTS that is synthetically derived from a known sequence that promotes an interaction with DNA. Such a DTS is within the scope of the present disclosure. Further, the skilled artisan may screen putative DTS sequences to provide an appropriate and functional DTS sequence, i.e. one that promotes an interaction with DNA. Such a DTS is within the scope of the present disclosure.

[0149] In some embodiments, the DTS is an SV40-DTS. In some embodiments, the DTS comprises a nucleic acid sequence that behaves substantially similar to an SV40-DTS. In some embodiments, the SV40-DTS comprises a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to GGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATC TCAATTAGTCAGCAACCA (SEQ ID NO: 8). In some embodiments, the SV40-DTS comprises a nucleic acid sequence of SEQ ID NO: 8.

[0150] In some embodiments the DTS or NLS regions further comprise at least one spacer located either before or after the DTS or NLS regions. If two spacers are present, they are located immediately before and after the DTS, NLS, or both. Spacers are generally known in the art and comprise a range of flexible or semi-flexible amino acids or molecules. In some embodiments, the spacer or spacers comprise a polyglycine, optionally with alanine and / or serine residues. In some embodiments, the spacer comprises an amino acid sequence selected from any one of GGGG (SEQ ID NO: 5) or GGGGGG (SEQ ID NO: 29). In some embodiments, the spacer comprises the amino acid sequence of SEQ ID NO: 5. In some embodiments, the spacer comprises the amino acid sequence of SEQ ID NO: 29. In some embodiments, the spacer or spacers comprise polyethylene glycol (PEG), propylene glycol alginate (PGA), PEG-polylactic acid (PLA), poly lactic-co-glycolic acid (PGLA), or any combination thereof. In some embodiments, the spacer or spacers comprise a saturated or unsaturated hydrocarbon chain comprising 3-6 carbons that can optionally be substituted.

[0151] In some embodiments, the adaptor molecule further comprises a cell penetrating peptide sequence (CPP). CPPs are a group of short peptides that have the ability to increase membrane transduction and can be used to assist the transportation of molecule through cell membrane (for review see, Xu et al., 2019, J Control Release, 309: 106-124). A wide range of CPPs may be included in the adaptor molecule to assist the DNA dendrimer-based composition to pass into a target cell or target nucleus. For example, in some embodiments, the CPP has an amino acid sequence of QPRRRPRRKKRG (SEQ ID NO: 6). In some embodiments, the CPP is located between the DBS and the cargo binding region.

[0152] In some embodiments, the cargo is separable from the DNA dendrimer. Thus, in some embodiments the adaptor molecule further comprises one or more cleavage sites. Cleavage sites may be located anywhere between the DBS and the cargo binding region. In some embodiments, the cleavage site is located adjacent to, or nearly adjacent to, the DBS. For example, in some embodiments, the cleavage site is a valine-citruline / p-aminobenzyl carbamate (val-cit) cleavable linker. Val-cit linkers are known in the art and are used in drug conjugation to release cargoes from targeting moieties. In the context of the provided exemplary sequences herein, a val-cit linker may be represented by the sequence VCit, wherein Cit is citroline. Other cleavable linkers known in the art may also be included, such as a ribozyme self-cleaving cleavage site, or tunable pH-sensitive linkers (see, e.g., Choy et al., Bioconjugate Chem. (2016) 27(3): 824-830).

[0153] In some embodiments, the adaptor molecule further comprises at least one flexible linker. In some embodiments, the flexible linker is located between the DNS and the cargo binding region. In some embodiments, the at least one flexible linker is or comprises polyethylene glycol (PEG), propylene glycol alginate (PGA), PEG-polylactic acid (PLA), poly lactic -co-glycolic acid (PGLA), (GG)n (SEQ ID NO: 31), (GGGGS)n (SEQ ID NO: 7), (GGGGA)n (SEQ ID NO: 27), or any combination thereof, wherein each n is independently, 1-5.

[0154] In some embodiments, the adaptor molecule comprises a purification region. In some embodiments, the purification region comprises an amino acid sequence of HHHHHHC (SEQ ID NO: 28).

[0155] Adaptor molecules provided for herein may have none, some, or all elements disclosure herein. In a non-limiting example, an adaptor molecule may comprise one or more purification regions, DTS, NLS, CPP, spacers, cleavage sites, flexible linkers, or any combination thereof, in addition to the DBS and cargo binding region. In some embodiments, an adaptor molecule comprises, in any order, any one, or any combination of DBS, flexible linker, CPP, NLS, purification region, spacer, and cargo binding region, such as those provided herein. Non-limiting examples of adaptor molecules are listed below and comprise in 5’ to 3’ direction, the following elements:

[0156] It is to be understood that the adaptor molecules recited in the preceding table are contiguous sequences comprising the various specific sequence identifiers. Accordingly, the adaptor molecule represented by the sequence TAGAGGTAACAACTAGCGTACAATTTTTTTTTT(SEQ ID NO: 4)-HHHHHHC(SEQ ID NO: 28) provided above is a contiguous sequence, wherein the 3’ terminal thymine of SEQ ID NO: 4 is conjugated to the N-terminal histidine of SEQ ID NO: 28, wherein the hyphen (-) separating the various portions of the contiguous sequence represent a conjugation.

[0157] The adaptor molecule represented by the sequence TAGAGGTAACAACTAGCGTACAATTTTTTTTTT(SEQ ID NO: 4)-GGGGGG(SEQ ID NO: 29)-YPDEVKRKKKP(SEQ ID NO: 1) provided above is a contiguous sequence, wherein the 3’ terminal thymine od SEQ ID NO: 4 is conjugated to the N-terminal glycine of SEQ ID NO: 29, and the C-terminal glycine of SEQ ID NO: 29 is conjugated to the N- terminal tyrosine of SEQ ID NO: 1, wherein the hyphen (-) separating the various portions of the contiguous sequence represent a conjugation. The adaptor molecule represented by the sequence TAGAGGTAACAACTAGCGTACAATTTTTTTTTT(SEQ ID NO: 4)-GGGGGG(SEQ ID NO: 29)-(VCit)-GGGG(SEQ ID NO: 5)-YPDEVKRKKKP(SEQ ID NO: 1)-GGGG(SEQ ID NO: 5)-HHHHHHC(SEQ ID NO: 28) provided above is a contiguous sequence, wherein the 3’ terminal thymine of SEQ ID NO: 4 is conjugated to the N-terminal glycine of SEQ ID NO: 29, the C-terminal glycine of SEQ ID NO: 29 is conjugated to a val-cit linker (VCit) which is in turn conjugated to the N-terminal glycine of SEQ ID NO: 5, the C-terminal glycine of SEQ ID NO: 5 is conjugated to the N-terminal tyrosine of SEQ ID NO: 1, the C-terminal proline of SEQ ID NO: 1 is conjugated to the N-terminal glycine of SEQ ID NO: 5, and the C- terminal glycine of SEQ ID NO: 5 is conjugated to the N-terminal histidine of SEQ ID NO: 28, wherein the hyphen (-) separating the various portions of the contiguous sequence represent a conjugation.

[0158] The adaptor molecule represented by the sequence TAGAGGTAACAACTAGCGTACAATTTTTTTTTT(SEQ ID NO: 4)-GGGGGG(SEQ ID NO: 29)-(VCit)-QPRRRPRRKKRG(SEQ ID NO: 6)- SLLESPFDKPDEVKRKKKPPTSHQSDATAEDDSSSKKK(SEQ ID NO: 2)-GGGG(SEQ ID NO: 5)-HHHHHHC(SEQ ID NO: 28) provided above is a contiguous sequence, wherein the 3’ terminal thymine of SEQ ID NO: 4 is conjugated to the N-terminal glycine of SEQ ID NO: 29, the C-terminal glycine of SEQ ID NO: 29 is conjugated to a val-cit linker (VCit) which is in turn conjugated to the N-terminal glutamine of SEQ ID NO: 6, the C-terminal glycine of SEQ ID NO: 6 is conjugated to the N-terminal serine of SEQ ID NO: 2, the C- terminal lysine of SEQ ID NO: 2 is conjugated to the N-terminal glycine of SEQ ID NO: 5, and the C-terminal glycine of SEQ ID NO: 5 is conjugated to the N-terminal histidine of SEQ ID NO: 28, wherein the hyphen (-) separating the various portions of the contiguous sequence represent a conjugation.

[0159] As provided for herein, the conjugation of protein-oligonucleotide, i.e. amino acid: - nucleic acid conjugations, are known in the art and any such conjugation technique may be utilized to construct the above mentioned adaptor molecules. Accordingly, the conjugation between the various portions of the contiguous sequence as represented by the hyphen (-) above may be any appropriate conjugation as known in the art and provided for herein

[0160] In some embodiments, an adaptor molecule comprises the sequences provided in the table below. In some embodiments, an adaptor molecule comprises, from 5’ to 3’ end of the nucleotide sequence and N-terminus to C-terminus of the amino acid sequence, the sequences provided in the table below.

[0161] In some embodiments, an adaptor molecule comprises, from 5’ to 3’ end, the sequences of SEQ ID NO: 4 and SEQ ID NO: 28. In some embodiments, an adaptor molecule comprises, from 5’ to 3’ end, the sequences of SEQ ID NO: 4, SEQ ID NO: 29, and SEQ ID NO: 1. In some embodiments, an adaptor molecule comprises, from 5’ to 3’ end, the sequences of SEQ ID NO: 4, SEQ ID NO: 29, VCit, SEQ ID NO: 5, SEQ ID NO: 1, SEQ ID NO: 5, and SEQ ID NO: 28. In some embodiments, an adaptor molecule comprises, from 5’ to 3’ end, the sequences of SEQ ID NO: 4, SEQ ID NO: 29, VCit, SEQ ID NO: 6, SEQ ID NO: 2, SEQ ID NO: 5, and SEQ ID NO: 28. In some embodiments, an adaptor molecule comprises, from 5’ to 3’ end, the sequences of SEQ ID NO: 4 and SEQ ID NO: 28, wherein the sequences are conjugated to each other. In some embodiments, an adaptor molecule comprises, from 5’ to 3’ end, the sequences of SEQ ID NO: 4, SEQ ID NO: 29, and SEQ ID NO: 1, wherein the sequences are conjugated to each other. In some embodiments, an adaptor molecule comprises, from 5’ to 3’ end, the sequences of SEQ ID NO: 4, SEQ ID NO: 29, VCit, SEQ ID NO: 5, SEQ ID NO: 1, SEQ ID NO: 5, and SEQ ID NO: 28, wherein the sequences are conjugated to each other. In some embodiments, an adaptor molecule comprises, from 5’ to 3’ end, the sequences of SEQ ID NO: 4, SEQ ID NO: 29, VCit, SEQ ID NO: 6, SEQ ID NO: 2, SEQ ID NO: 5, and SEQ ID NO: 28, wherein the sequences are conjugated to each other.

[0162] E. Support Molecules

[0163] The compositions herein may also comprise one or more support molecules. Support molecules as provided for herein can be used for a range of tasks, including, but not limited to, protecting DNA dendrimers and cargo polynucleotides from nuclease degradation, enhancing transfection efficiency, assisting in nuclear delivery, and condensing the size of the DNA dendrimer, cargo polynucleotide, or both. Support molecules can be covalently or non- covalently linked to the DNA dendrimer in the same or similar manner as the targeting moieties and cargos. However, in some embodiments, one or more support molecules are not linked to the DNA dendrimer and can associate with the composition through other means.

[0164] Without wishing to be bound by theory, because many polynucleotide structures have a negatively changed amine backbone, a support molecule with a sufficient positive charge can associate with the composition through charge attraction. Thus, in some embodiments, the one or more support molecules associate with the composition through charge attraction. In some embodiments, the one or more support molecules have a net-positive charge that is high enough to allow for the one or more support molecules to interact with and, optionally, compact the negatively charged DNA dendrimer. In some embodiments, the one or more support molecules have a net-positive charge that is low enough to avoid aggregation or other cytotoxic side effects.

[0165] Additionally, such support molecules can also associate with cargo polynucleotides and DNA dendrimers simultaneously. Thus, in some embodiments, compositions provided for herein comprise a cargo polynucleotide, a support molecule, and a DNA dendrimer linked to a targeting moiety, wherein the cargo polynucleotide is not covalently linked to the DNA dendrimer. The support molecule can associate the cargo polynucleotide with the DNA dendrimer in this way regardless of the topology of the cargo polynucleotide. However, when the cargo polynucleotide has a full circular topology, without any nicks, sites, or regions for direct covalent linkage to a DNA dendrimer or an adaptor molecule, the one or more support molecule can associate the cargo polynucleotide and the DNA dendrimer together to form the composition.

[0166] Support molecules are provided for herein can be used individually, as repeats, or in combination either within one molecular entity or a complex mixture of individual molecular entities. In some embodiments, support molecules can be added to the composition prior to the association of the cargo, DNA dendrimer, and optionally, the adaptor molecule. In some embodiments, support molecules can be added to the composition after the association of the cargo, DNA dendrimer, and optionally, the adaptor molecule. In some embodiments, and without limitation, support molecules provided herein are stabilizers.

[0167] Without wishing to be bound by a particular theory, pore sizes vary from cell type to cell type and only permit materials of the same size to be taken up. To enable delivery to cells with smaller pore sizes, the particle must be reduced or compacted. In addition to size, particle size and particle protection can increase durability of the scaffold and payload. So far, a variety of stabilizer moieties have been developed and tested to both compact nanoparticles and shield them from degrading enzymes. Net-positive charge allows for the stabilizer to interact and compact the negatively charged nucleic acids through electrostatic interactions. This compaction allows for protection against nucleases since the stabilizer is now at the surface of the nanostructure which interacts with the in vivo environment. The charge must be enough to complex the nucleic acids but not high enough to cause aggregation or other cytotoxic side effects brought on due to positive charge. Thus, the stabilizer can be comprised of biocompatible peptides and / or polymers. The term “biocompatible”, as used herein, refers to a substance that has minimal toxicity in vitro / in vivo, is excretable and / or can degrade into processable units by the body. Thus, in some embodiments, the stabilizer comprises peptide portions that enhance cellular uptake and nuclear localization. CPPs sequences and NLS sequences are elements added into the stabilizer sequences if the initial base stabilizer (positively-charged compaction portion only) is successful at compacting the nucleic acids and protects against nucleases.

[0168] In some embodiments, a stabilizer is a support molecule. In some embodiments, a support molecule comprises biocompatible peptides, polymers, or both. Thus, in some embodiments, the support molecule is a peptide-based support molecule or a polymer-based support molecule. In some embodiments, a support molecule comprises a CPP sequence, a NLS sequence, or both. In some embodiments, the CPP sequence is any CPP sequence disclosed herein. In some embodiments, the NLS sequence is any NLS sequence disclosed herein. In some embodiments, the stabilizer is a peptide-based stabilizer. In some embodiments, the support molecule is a peptide-based support molecule. In some embodiments, the support molecule comprises an amino acid sequence selected from any one of: ATPKKSTKKTPKKAKKATPKKSTKKTPKKAKK (histone Hl sequence, SEQ ID NO: 12); WRRRGFGRRR (SEQ ID NO: 13); GRKKRRQRRRPQ (SEQ ID NO: 14); PKKKRKV (SV40 NLS sequence, SEQ ID NO: 15); GLFHAIAHFIHGGWHGLIHGWYG (SEQ ID NO: 16); WEAALAEALAEALAEHLAEALAEALEALAA (SEQ ID NO: 17); HHHHHHHHHH (SEQ ID NO: 18); (KK)n (SEQ ID NO: 32), where n = 2-15; GLFHAIAHFIHGGWHGLIHGWYGP (H5WYG sequence, SEQ ID NO: 9); WSQ (spacer sequence); AEAEAKAKAEAEAKAK (SEQ ID NO: 33), AEAEAEAEAKAKAKAK (SEQ ID NO: 34); GLFHAIAHFIHGGWHGLIHGWYGWSQPPKKKRKVATPKKSTKKTPKKAKKATPKKS TKKTPKKAKKATPKKSTKKTPKKAKKATPKKSTKKTPKKAKK (SEQ ID NO: 35), ATPKKSTKKTPKKAKKATPKKSTKKTPKKAKKATPKKSTKKTPKKAKKATPKKSTK KTPKKAKK (SEQ ID NO: 36), THRPPMWSPVWP-(VCit)-

[0169] ATPKKSTKKTPKKAKKATPKKSTKKTPKKAKKGGGGSKKPNKKKRKE (SEQ ID NO:

[0170] 37), THRPPMWSPVWP-(VCit)- ATPKKSTKKTPKKAKKATPKKSTKKTPKKAKKGGGGSPKKKRKVC (SEQ ID NO:

[0171] 38), THRPPMWSPVWP-(VCit)-ATPKKSTKKTPKKAKKATPKKSTKKTPKKAKKC (SEQ ID NO: 39), ATPKKSTKKTPKKAKKATPKKSTKKTPKKAKKGGGGSPKKKRKV (SEQ ID NO: 40), ATPKKSTKKTPKKAKKATPKKSTKKTPKKAKKGGGGSKKPNKKKRKE (SEQ ID NO: 41), THRPPMWSPVWP (SEQ ID NO: 42), or any combination thereof. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one, or any combination of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, and 42. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 9. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 12. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 13. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 14. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 15. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 16. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 17. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 18. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 32. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 33. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 34. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 35. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 36. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 37. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 38. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 39. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 40. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 41. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 42. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 12. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 13. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 14. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 15. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 16. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 17. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 18. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 32. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 33. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 34. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 35. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 36. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 37. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 38. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 39. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 40. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 41. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 42. In some embodiments, the support molecule comprises an amino acid sequence of WSQ.

[0172] In some embodiments, the support molecule comprises an amino acid sequence selected from any one of: GLFHAIAHFIHGGWHGLIHGWYGWSQPPKKKRKVATPKKSTKKTPKKAKKATPKKS TKKTPKKAKK (SEQ ID NO: 19);

[0173] HHHHHHHHHHATPKKSTKKTPKKAKKATPKKSTKKTPKKAKK (SEQ ID NO: 20); or GLFHAIAHFIHGGWHGLIHGWYGWSQPPKKKRKVGRKKRRQRRRPQWRRRGFGRR R (SEQ ID NO: 21). In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 19, 20, or 21. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 19. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 20. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 21. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 19. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 20. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 21.

[0174] In some embodiments, the stabilizer is a polymer-based stabilizer. In some embodiments, the support molecule is a polymer-based support molecule. In some embodiments, the support molecule is a lysine-based support molecule. In some embodiments, the support molecule is a lysine polymer support molecule. In some embodiments, a support molecule comprises an amino acid sequence selected from any one of: KKKKKKKKKKKKKKKKKKK (SEQ ID NO: 24); KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK (SEQ ID NO: 25); or KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK KKKKKKKKKK (SEQ ID NO: 26). In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 24, 25, or 26. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 24. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 25. In some embodiments, the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 26. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 24. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 25. In some embodiments, the support molecule comprises an amino acid sequence of SEQ ID NO: 26.

[0175] In some embodiments, any of the support molecules provided for herein may further comprise additional moieties, such as but not limited to visualization moieties or moieties to support further chemical modification. In some non-limiting embodiments, the visualization moiety is Cy3, or any other small molecule fhiorophore known in the art. In some nonlimiting embodiments, the moiety to support further chemical modification is dibenzylcyclooctyne (DBCO) or the like. The visualization moieties may be attached at the N-terminus, C-terminus, or both the N and C-terminus of the support molecule. Likewise, the chemical modification moieties may be attached at the N-terminus, C-terminus, or both the N and C-terminus of the support molecule. The visualization and / or chemical modification moieties may be conjugated directly to the support molecule, or they may be conjugated through a cleavable linker, such as a val-cit linker as provided for herein.

[0176] In some embodiments, a support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 37 further comprises a visualization moiety on the N-terminus, the C-terminus, or both the N-terminus and C-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on the N-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on the C-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on both the N-terminus and C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 37 and a visualization moiety is given by the sequence: THRPPMWSPVWP-(VCit)- ATPKKSTKKTPKKAKKATPKKSTKKTPKKAKKGGGGSKKPNKKKRKE-Cy3 (SEQ ID NO: 44).

[0177] In some embodiments, a support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 38 further comprises a visualization moiety on the N-terminus, the C-terminus, or both the N-terminus and C-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on the N-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on the C-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on both the N-terminus and C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 38 and a visualization moiety is given by the sequence: THRPPMWSPVWP-(VCit)- ATPKKSTKKTPKKAKKATPKKSTKKTPKKAKKGGGGSPKKKRKVC-Cy3 (SEQ ID NO: 45).

[0178] In some embodiments, a support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 39 further comprises a visualization moiety on the N-terminus, the C-terminus, or both the N-terminus and C-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on the N-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on the C-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on both the N-terminus and C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 39 and a visualization moiety is given by the sequence: THRPPMWSPVWP-(VCit)- ATPKKSTKKTPKKAKKATPKKSTKKTPKKAKKC-Cy3 (SEQ ID NO: 46).

[0179] In some embodiments, a support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 40 further comprises a visualization moiety, a chemical modification moiety, or a combination thereof. In some embodiments, the support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 40 further comprises a visualization moiety on the N-terminus, the C-terminus, or both the N-terminus and C-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on the N-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on the C-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on both the N-terminus and C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 40 further comprises a chemical modification moiety on the N-terminus, the C-terminus, or both the N- terminus and C-terminus of the amino acid sequence. In some embodiments, the chemical modification moiety is on the N-terminus of the amino acid sequence. In some embodiments, the chemical modification moiety is on the C-terminus of the amino acid sequence. In some embodiments, the chemical modification moiety is on both the N-terminus and C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 40 further comprises both a visualization moiety and a chemical modification moiety. In some embodiments, the visualization moiety is on the N-terminus of the amino acid sequence and the chemical modification moiety is on the C-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on the C-terminus of the amino acid sequence and the chemical modification moiety is on the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 40 and both a visualization moiety and a chemical modification moiety is given by the sequence: DBCO-(VCit)-ATPKKSTKKTPKKAKKATPKKSTKKTPKKAKKGGGGSPKKKRKV- Cy3 (SEQ ID NO: 47).

[0180] In some embodiments, a support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 41 further comprises a visualization moiety, a chemical modification moiety, or a combination thereof. In some embodiments, the support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 41 further comprises a visualization moiety on the N-terminus, the C-terminus, or both the N-terminus and C-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on the N-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on the C-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on both the N-terminus and C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 41 further comprises a chemical modification moiety on the N-terminus, the C-terminus, or both the N- terminus and C-terminus of the amino acid sequence. In some embodiments, the chemical modification moiety is on the N-terminus of the amino acid sequence. In some embodiments, the chemical modification moiety is on the C-terminus of the amino acid sequence. In some embodiments, the chemical modification moiety is on both the N-terminus and C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 41 further comprises both a visualization moiety and a chemical modification moiety. In some embodiments, the visualization moiety is on the N-terminus of the amino acid sequence and the chemical modification moiety is on the C-terminus of the amino acid sequence. In some embodiments, the visualization moiety is on the C-terminus of the amino acid sequence and the chemical modification moiety is on the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 41 and both a visualization moiety and a chemical modification moiety is given by the sequence: DBCO-(VCit)-

[0181] ATPKKSTKKTPKKAKKATPKKSTKKTPKKAKKGGGGSKKPNKKKRKE-Cy3 (SEQ ID NO: 48).

[0182] In some embodiments, polyethylene glycol (PEG) can be linked or conjugated to any support molecule disclosed herein. The PEG molecule can be any known PEG in the art, including a variety of molecular weights. In some embodiments, the PEG is PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000. In some embodiments, the PEG is PEG400. In some embodiments, the PEG is PEG500. In some embodiments, the PEG is PEG 1000. In some embodiments, the PEG is PEG2000. In some embodiments, the PEG is PEG3000. In some embodiments, the PEG is PEG4000. In some embodiments, the PEG is PEG-5000. In some embodiments, the combination of the PEG molecule and the support molecule increases circulation time of the support molecule, shields positive charges, enhances stability of the composition, or any combination thereof. In some embodiments, the PEG molecule is attached to the N-terminus of the support molecule. In some embodiments, the PEG molecule is attached to the C-terminus of the support molecule.

[0183] In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 9 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 12 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 13 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 14 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 15 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 16 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 17 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 18 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 19 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 20 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 21 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 24 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 25 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 26 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 32 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 33 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 34 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 35 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 36 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 37 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 38 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 39 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 40 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 41 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 42 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 43 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 44 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 45 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 46 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 47 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 48 further comprises a PEG molecule. In some embodiments, the support molecule comprises an amino acid sequence of WSQ and further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 and a PEG molecule further comprises one or more spacer molecules. In some embodiments, the spacer molecule is as provided for herein. In some embodiments, the spacer molecule comprises an amino acid sequence of SEQ ID NO: 5. In some embodiments, the spacer molecule comprises an amino acid sequence of WSQ.

[0184] In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 9 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 12 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 13 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 14 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 15 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 16 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 17 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 18 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 19 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 20 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 21 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 24 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 25 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 26 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 32 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 33 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 34 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 35 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 36 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 37 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 38 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 39 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 40 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 41 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 42 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 43 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 44 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 45 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 46 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 47 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 48 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 and a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule further comprises one or more spacer molecules. In some embodiments, the spacer molecule is as provided for herein. In some embodiments, the spacer molecule comprises an amino acid sequence of SEQ ID NO: 5. In some embodiments, the spacer molecule comprises an amino acid sequence of WSQ.

[0185] In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 9 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 12 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 13 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 14 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 15 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 16 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 17 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 18 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 19 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 20 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 21 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 24 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 25 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 26 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 32 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 33 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 34 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 35 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 36 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 37 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 38 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 39 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 40 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 41 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 42 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 43 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 44 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 45 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 46 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 47 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 48 further comprises a PEG2000 molecule. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 and a PEG2000 molecule further comprises one or more spacer molecules. In some embodiments, the spacer molecule is as provided for herein. In some embodiments, the spacer molecule comprises an amino acid sequence of SEQ ID NO: 5. In some embodiments, the spacer molecule comprises an amino acid sequence of WSQ.

[0186] In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 further comprises a PEG molecule linked or conjugated at the N-terminus or the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus or the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or

[0187] PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 and a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus or the C-terminus of the amino acid sequence further comprises one or more spacer molecules. In some embodiments, the spacer molecule is as provided for herein. In some embodiments, the spacer molecule comprises an amino acid sequence of SEQ ID NO: 5. In some embodiments, the spacer molecule comprises an amino acid sequence of WSQ.

[0188] In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 9 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 12 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 13 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 14 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 15 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 16 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 17 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 18 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 19 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 20 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 21 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 24 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 25 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N- terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 26 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N- terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 32 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 33 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 34 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 35 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 36 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 37 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 38 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 39 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 40 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 41 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 42 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 43 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 44 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 45 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 46 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 47 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 48 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 and a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the N-terminus of the amino acid sequence further comprises one or more spacer molecules. In some embodiments, the spacer molecule is as provided for herein. In some embodiments, the spacer molecule comprises an amino acid sequence of SEQ ID NO: 5. In some embodiments, the spacer molecule comprises an amino acid sequence of WSQ.

[0189] In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 9 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 12 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 13 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 14 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 15 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 16 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 17 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 18 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 19 further comprises a PEG2000 molecule linked or conjugated at the N- terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 20 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 21 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 24 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 25 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 26 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 32 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 33 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 34 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 35 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 36 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 37 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 38 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 39 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 40 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 41 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 42 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 43 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 44 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 45 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 46 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 47 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 48 further comprises a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 and a PEG2000 molecule linked or conjugated at the N-terminus of the amino acid sequence further comprises one or more spacer molecules. In some embodiments, the spacer molecule is as provided for herein. In some embodiments, the spacer molecule comprises an amino acid sequence of SEQ ID NO: 5. In some embodiments, the spacer molecule comprises an amino acid sequence of WSQ.

[0190] In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 9 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 12 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 13 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 14 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 15 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 16 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 17 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 18 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 19 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 20 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 21 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 24 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 25 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 26 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 32 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 33 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 34 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 35 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 36 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 37 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 38 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 39 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 40 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 41 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 42 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 43 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 44 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 45 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 46 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 47 further comprises a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 48 further comprises a PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 and a PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000 molecule linked or conjugated at the C-terminus of the amino acid sequence further comprises one or more spacer molecules. In some embodiments, the spacer molecule is as provided for herein. In some embodiments, the spacer molecule comprises an amino acid sequence of SEQ ID NO: 5. In some embodiments, the spacer molecule comprises an amino acid sequence of WSQ.

[0191] In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 9 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 12 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 13 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 14 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 15 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 16 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 17 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 18 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 19 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 20 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 21 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 24 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 25 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 26 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 32 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 33 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 34 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 35 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 36 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 37 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 38 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 39 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 40 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 41 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 42 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 43 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 44 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 45 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 46 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 47 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 48 further comprises a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence. In some embodiments, the support molecule comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, or 48 and a PEG2000 molecule linked or conjugated at the C-terminus of the amino acid sequence further comprises one or more spacer molecules. In some embodiments, the spacer molecule is as provided for herein. In some embodiments, the spacer molecule comprises an amino acid sequence of SEQ ID NO: 5. In some embodiments, the spacer molecule comprises an amino acid sequence of WSQ.

[0192] In some embodiments, the support molecule comprising an amino acid sequence of any one of SEQ ID NOs: 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 9 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 12 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 13 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 14 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 15 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 16 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 17 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 18 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 19 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 20 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 21 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 24 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 25 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 26 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 32 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 33 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 34 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 35 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 36 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 37 further comprises a PEG molecule. In some embodiments, the support molecule comprising an amino acid sequence of SEQ ID NO: 38 further compris...

Claims

WHAT IS CLAIMED IS:

1. A composition comprising: a DNA dendrimer; a targeting moiety; and an adaptor molecule-cargo polynucleotide complex, wherein the DNA dendrimer is linked to, conjugated to, or associated with the targeting moiety and the adaptor molecule-cargo polynucleotide complex.

2. The composition of claim 1 , wherein the adaptor molecule-cargo polynucleotide complex comprises an adaptor molecule and a cargo polynucleotide.

3. The composition of claim 2, wherein the cargo polynucleotide comprises at least one promoter and at least one coding sequence encoding for at least one molecule of interest, wherein the cargo polynucleotide is a nicked circular polynucleotide, a linear polynucleotide with a closed 5' and 3' end, a linear polynucleotide with open 5' and 3' ends, or a linear polynucleotide with one open and one closed end, wherein the one open and one closed end can be at either the 5' and 3' of the polynucleotide.

4. The composition of claim 2, wherein the cargo polynucleotide further comprises at least one DNA targeting sequence (DTS).

5. The composition of claim 4, wherein the cargo polynucleotide comprises two or more DTSs.

6. The composition of claim 2, wherein the cargo polynucleotide further comprises at least one nuclear localization signal sequence (NLS).

7. The composition of claim 4, wherein the cargo polynucleotide comprises at least one DTS and at least one NLS.

8. The composition of claim 2, wherein the adaptor molecule comprises a DNA dendrimer binding sequence (DBS) and a cargo binding region (CBR).

9. The composition of claim 8, wherein the adaptor is linked to the DNA dendrimer through the DBS, wherein the DBS comprises a nucleic acid sequence that is complimentary to a nucleic acid sequence on the DNA dendrimer.

10. The composition of claim 8, wherein the DBS comprises a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NOs: 3, 4, 10 , 11, 22, or 23.

11. The composition of claim 8, wherein the adaptor molecule further comprises a tag, such as, for example, a tag that can be used as an affinity tag to isolate / purify the composition complex.

12. The composition of claim 8, wherein the adaptor molecule further comprises at least one NLS, wherein the at least one NLS is located between or overlaps with the DBS and the cargo binding region.

13. The composition of claim 12, wherein the at least one NLS comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NO: 1, 2, 15, or 43.

14. The composition of claims 12, wherein the at least one NLS further comprises at least one spacer located before or after the at least one NLS, wherein the at least one spacer comprises polyethylene glycol (PEG), propylene glycol alginate (PGA), PEG-polylactic acid (PL A), poly lactic -co-glycolic acid (PGLA), a glycine / alanine spacer, a glycine / serine spacer, or any combination thereof.

15. The composition of claim 14, wherein the at least one spacer comprises the amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NO: 5 or 29.

16. The composition of claim 8, wherein the adaptor molecule further comprises at least one DTS, wherein the at least one DTS is located between or overlaps with the DBS and the CBR.

17. The composition of claim 8, wherein the adaptor molecule further comprises a cell penetrating peptide sequence (CPP), wherein the CPP is located between or overlapping with the DBS and the CBR.

18. The composition of claim 17, wherein the CPP comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to SEQ ID NO: 6.

19. The composition of claim 8, wherein the adaptor molecule further comprises at least one cleavage site.

20. The composition of claim 19, wherein the cleavage site is a val-cit linker.

21. The composition of claim 8, wherein the adaptor molecule further comprises at least one flexible linker selected from the group consisting of polyethylene glycol (PEG),propylene glycol alginate (PGA), PEG-polylactic acid (PLA), poly lactic-co-glycolic acid (PGLA), (GG)n, (GGGGS)n, or (GGGGA)n, wherein each n is, independently, 1-5.

22. The composition of claim 1, wherein the composition further comprises a support molecule.

23. The composition of claim 22, wherein the support molecule is or is not linked or conjugated to the DNA dendrimer.

24. The composition of claim 22, wherein the support molecule: i) condenses the size of the cargo polynucleotide, the DNA dendrimer, or both; ii) molecule assists in nuclear delivery; iii) protects the cargo polynucleotide, the DNA dendrimer, or both, from nuclease degradation; and / or iv) enhances the transfection efficiency of the composition.

25. The composition of claim 22, wherein the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NO: 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48, or any combination thereof.

26. The composition of claims 22, wherein the support molecule further comprises a PEG molecule linked or conjugated at N-terminus or C-terminus of the amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NO: 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48, or any combination thereof.

27. The composition of claim 26, wherein the PEG molecule is selected from any one of PEG400, PEG500, PEG 1000, PEG2000, PEG3000, PEG4000, or PEG-5000.

28. The composition of any one of claims 1-27, wherein the targeting moiety is selected from the group consisting of an antibody, a naturally-occurring ligand for the receptor or a functional derivative thereof, a vitamin, a hormone, a small molecule mimetic of a naturally- occurring ligand, a peptide, a polypeptide, a peptidomimetic, a carbohydrate, a lipid, an aptamer, a nucleic acid, a toxin, a component of a microorganism, any other molecule provided it binds specifically to the cell surface molecule and induces endocytosis of the bound moiety, or any combination thereof.

29. A composition comprising a cargo polynucleotide, a support molecule, and a DNA dendrimer linked to a targeting moiety.

30. The composition of claim 29, wherein the targeting moiety is selected from the group consisting of an antibody, a naturally-occurring ligand for the receptor or a functional derivative thereof, a vitamin, a hormone, a small molecule mimetic of a naturally-occurring ligand, a peptide, a polypeptide, a peptidomimetic, a carbohydrate, a lipid, an aptamer, a nucleic acid, a toxin, a component of a microorganism, any other molecule provided it binds specifically to the cell surface molecule and induces endocytosis of the bound moiety, or any combination thereof.

31. The composition of claim 29, wherein: the cargo polynucleotide comprises at least one promoter and at least one coding sequence encoding for at least one molecule of interest, and, optionally, a DBS, wherein the cargo polynucleotide is full circular polynucleotide (e.g., plasmid), nicked circular polynucleotide, a linear polynucleotide with closed 5' and 3' end, a linear polynucleotide with open 5' and 3' ends, or a linear polynucleotide with one open and one closed end, wherein the one open and one closed end can be at either the 5' and 3' of the cargo polynucleotide.

32. The composition of claim 31 , wherein the cargo polynucleotide a closed circle polynucleotide or a nicked circular polynucleotide.

33. The composition of claim 29, wherein the cargo polynucleotide further comprises at least one DTS.

34. The composition of claim 33, wherein the cargo polynucleotide is a nicked circular polynucleotide, and the DTS is linked to the cargo polynucleotide at the single stranded DNA break (i.e., the location of the nick).

35. The composition of claim 29, wherein the cargo polynucleotide further comprises at least one NLS.

36. The composition of claim 29, wherein the cargo polynucleotide comprises at least one DTS and at least one NLS.

37. The composition of claim 31, wherein the DBS comprises a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NO: 3, 4, 10, 11, 22, or 23.

38. The composition of claim 29, wherein the support molecule is or is not linked or conjugated to the DNA dendrimer.

39. The composition of claim 29, wherein the support molecule: i) condenses the size of the cargo polynucleotide, the DNA dendrimer, or both; ii) assists in nuclear delivery; iii) protects the cargo polynucleotide, the DNA dendrimer, or both from nuclease degradation; and / or iv) enhances the transfection efficiency of the composition.

40. The composition of claim 29, wherein the presence of the support molecule facilitates the association of the cargo polynucleotide and the DNA dendrimer to each other.

41. The composition of claim 29, wherein the support molecule has a positive charge.

42. The composition of claim 29, wherein the support molecule comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NO: 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48, or any combination thereof.

43. The composition of claim 29, wherein the support molecule further comprises a PEG molecule linked or conjugated at N-terminus or C-terminus of the amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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% sequence identity to any one of SEQ ID NO: 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48, or any combination thereof.

44. The composition of claim 43, wherein the PEG molecule is selected from any one of PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000, or PEG-5000.

45. The composition of any one of claims 1-44, wherein the coding sequence of the cargo polynucleotide encodes for an antibody, an enzyme, a protein, a miRNA, a siRNA, an antisense RNA, and the like.

46. The compositions of claim 22 or 29, wherein the nitrogen / phosphate (N / P) ratio of the support molecule is between 0.5 and 10.

47. A pharmaceutical composition comprising a composition of any one of claims 1-46 and a pharmaceutically acceptable carrier.

48. A method of delivering a molecule of interest to the nucleus of a target cell, the method comprising contacting the target cell with the composition of any one of claims 1-46 or the pharmaceutical composition of claim 47, wherein the targeting moiety binds to the target cell.

49. A method of treating a disease, the method comprising administering the composition of any one of claims 1-46 or the pharmaceutical composition of claim 47 to a subject to treat the disease, wherein the targeting moiety binds to the target cell.

50. A plasmid comprising a plasmid backbone comprising at least two enzyme restriction recognition sites, at least one promoter, at least one coding sequence encoding for at least one molecule of interest, and, optionally, a DBS, wherein the plasmid is capable of forming a cargo polynucleotide with various structures depending on whether the plasmid has one or more, or none of, a 5' end and a 3' end.

51. A method of manufacturing the composition of any one of claims 1-28, the method comprising: contacting the plasmid of claim 50 with one or more restriction enzymes that cut at the restriction enzyme recognition sites to form a nicked circular polynucleotide, a linear polynucleotide with a closed 5' and 3' end, a linear polynucleotide with open 5' and 3' ends, or a linear polynucleotide with one open and one closed end, linking the cargo polynucleotide to the adaptor molecule to form an adaptor moleculecargo polynucleotide complex, and linking the adaptor molecule- cargo polynucleotide complex and a targeting moiety to a DNA dendrimer to form the composition.

52. A method of manufacturing the composition of any one of claims 29-46, the method comprising: contacting the plasmid of claim 50 that comprise a DNA dendrimer binding sequence (DBS) with one or more restriction enzymes that cut at the restriction enzyme recognition sites to form a nicked circular polynucleotide, a linear polynucleotide with a closed 5' and 3'end, a linear polynucleotide with open 5' and 3' ends, or a linear polynucleotide with one open and one closed end, and linking the cargo polynucleotide and a targeting moiety to a DNA dendrimer to form the composition.

53. A method of manufacturing the composition of any one of claims 29-46, the method comprising contacting a circular uncut plasmid of claim 50 with a DNA dendrimer linked to a targeting moiety with a support molecule capable of condensing the size of the cargo polynucleotide and the DNA dendrimer, such that the cargo polynucleotide and the DNA dendrimer are associated together to form the composition.

54. A kit comprising a composition of claims 1-46, a pharmaceutical composition of claim 47, a plasmid of claim 50, or some combination thereof.

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