Compositions for delivery of cargo to cells

Abstract

The invention provides compositions for delivery of cargo to cells. The invention also provides compositions that bind multiple agents simultaneously. The compositions are useful as therapeutics. Methods of using the compositions are also provided.

1 - 20 . (canceled) 
     
     
         21 . A composition comprising:
 a DNA nanoparticle; and   at least one nucleic acid encoding a gene product that is expressed in a target cell, the at least one nucleic acid being linked to the DNA nanoparticle.   
     
     
         22 . The composition of  claim 21 , comprising at least two DNA nanoparticles, wherein the at least one nucleic acid is linked to each of the at least two DNA nanoparticles. 
     
     
         23 . The composition of  claim 21 , wherein the at least one nucleic acid is mRNA. 
     
     
         24 . The composition of  claim 23 , wherein the DNA nanoparticle comprises a 3′ end comprising at least two consecutive thymidine residues. 
     
     
         25 . The composition of  claim 24 , wherein the mRNA is linked to the DNA nanoparticle via the 3′ end of the DNA nanoparticle 
     
     
         26 . The composition of  claim 23 , wherein the DNA nanoparticle binds to a complementary sequence in the mRNA, the complementary sequence comprising at least two consecutive nucleic acid residues. 
     
     
         27 . The composition of  claim 21 , wherein the at least one nucleic acid is DNA. 
     
     
         28 . The composition of  claim 27 , wherein the at least one nucleic acid is a plasmid. 
     
     
         29 . The composition of  claim 21 , wherein the gene product is a polypeptide or protein. 
     
     
         30 . The composition of  claim 29 , wherein the polypeptide is a receptor that is expressed on a surface of the target cell. 
     
     
         31 . The composition of  claim 30 , wherein the receptor is a chimeric antigen receptor. 
     
     
         32 . The composition of  claim 21 , further comprising:
 a targeting moiety that binds to a target on a surface of the target cell, the target moiety being linked to the DNA nanoparticle.   
     
     
         33 . The composition of  claim 32 , wherein the targeting moiety is selected from the group consisting of an antibody, aptamer, ligand, nucleic acid, peptide, protein, and receptor. 
     
     
         34 . The composition of  claim 33 , wherein the targeting moiety is an aptamer. 
     
     
         35 . The composition of  claim 34 , wherein the aptamer comprises one or more modified nucleotides. 
     
     
         36 . The composition of  claim 35 , wherein the one or more modified nucleotides comprise at least one selected from the group consisting of a 2′ fluoro, 2′ O-methyl, 2-thiouridine, 2′-O-methoxyethyl, 2′-amine, 5-methoxyuridine, pseudouridine, 5-methylcytidine, N1-methyl-pseudouridine, locked nucleic acid (LNA), morpholino, and phosphorothioate modification. 
     
     
         37 . The composition of  claim 32 , wherein the target is selected from the group consisting of 5T4, ALDH1, alpha V beta 6 integrin, ARMX3, AXL, B2MG, BCMA, C4.4A, CA6, CA9, Cadherin 6, CAIX, carcinoembryonic antigen (CEA), CCR1, CCR10, CCR4, CCR5, CCR6, CCR8, CD1d, CD3, CD4, CD S, CD8, CD9, CD11c, CD13, CD14, CD15, CD16, CD16A, CD19, CD20, CD22, CD25, CD27, CD28, CD30, CD31, CD32, CD32B, CD33, CD34, CD37, CD38, CD39, CD41, CD44, CD44v6, CD45R, CD45RA, CD45RO, CD47, CD49b, CD51, CD54, CD56, CD57, CD61, CD62, CD62E, CD62L, CD64, CD66b, CD69, CD70, CD74, CD79B, CD79 alpha/beta, CD80, CD81, CD83, CD86, CD94/NKG2, CD103, CD117, CD119, CD123, CD127, CD133, CD134, CD137, CD138, CD146, CD154, CD160, CD161/NK1.1, CD164, CD171, CD172a, CD180, CD194, CD197, CD202b, CD205, CD206, CD207, CD215, CD223, CD235a, CD252, CD268, CD269, CD272, CD273, CD282, CD284, CD307d, CD309, CD317, CD326, CD369, CD370, c-Kit, c-MET, Criptoprotein, Crth2, CTLA-R, CXCR3, CXCR4, CXCR5, DCIR2, DEP1, DLL3, EBP50, EDG-1/S1P1, EDNRB, EFNA4, EGFR, EGFRvIII, EMR1, ENPP3, epithelial cell adhesion molecule (EpCAM), EphA2, ErbB, ErbB2, FAP, Fas ligand, FGFR2, FGFR3, fibroblast activation protein (FAP), FLT3, folate receptor-alpha, GARP, GD2, GITR, glypican 3, gp100, gpA33, GPC3, GPNMB, GUCY2C, HGF, HER2, HER3, HLA-DR, IFN-gamma R, IgG, IGF-1R, IL-1 R5, IL-1 RI, IL-6R, IL-6 R alpha, IL-13 receptor α, IL-18R alpha, IL-21 R, IL-23 R, kappa light chain, KIR Family, L1 cell adhesion molecule (L1CAM), LAMP-1, LANCL1, LAP, Lewis Y, LFA-1, LIV-1, LRRC15, MAGE family members, mesothelin, MET, MHCII, MSLN, MUC1, MUC16, NaPi2b, Nectin-4, NKG2D, NOTCH3, NTAL, NY-ESO-1, p-CAD, PD-1, PDGFR, PLD3, prostate specific cancer antigen (PSCA), prostate-specific membrane antigen (PSMA), PTK7, RORI, S1, Siglec-H, SLC44A4, SLITRK6, STEAP1, STX4, TCR alpha/beta, TF, TGFB RII, TGM2, TIM-1, TLR1, TLR2, TLR6, TLR7, TLR10, TNFSF7, TROP-2, VAMP3, VEGFR, VEGF-R2, vimentin, and VPS26A. 
     
     
         38 . The composition of  claim 21 , further comprising:
 a first targeting moiety that binds to a first target on a surface of the target cell, the first target moiety being linked to the DNA nanoparticle; and   a second targeting moiety that binds to a second target on a surface of the target cell, the second targeting moiety being linked to the DNA nanoparticle and being different from the first targeting moiety.   
     
     
         39 . The composition of  claim 38 , wherein the first targeting moiety and the second targeting moieties are aptamers. 
     
     
         40 . The composition of  claim 27 , wherein the DNA nanoparticle binds to a complementary sequence in the DNA, the complementary sequence comprising at least two consecutive nucleic acid residues.