RECOMBINANT ADENO-ASSOCIATED VIRUS VECTORS

1 . An adeno-associated virus (AAV) vector comprising (i) a recombinant capsid protein and (ii) a cargo nucleic acid encapsidated by the capsid protein, wherein the capsid protein comprises a peptide having the sequence of any one of SEQ ID NO: 12-20.

2 . The AAV vector of claim 1 , wherein the cargo nucleic acid comprises 5′ and 3′ AAV inverted terminal repeats.

3 . The AAV vector of claim 1 or 2 , wherein the cargo nucleic acid comprises a transgene.

4 . The AAV vector of claim 3 , wherein the transgene encodes a therapeutic protein or RNA.

5 . The AAV vector of any one of claims 1 - 4 , wherein the recombinant capsid protein has at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the native sequence of the AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAVrh.8, AAVrh.10, AAVrh32.33, AAVrh74, bovine AAV or avian AAV capsid.

6 . The AAV vector of claim 5 , wherein the recombinant capsid protein has at least 90% sequence identity to the native sequence of the AAV9 capsid.

7 . The AAV vector of any one of claims 1 - 6 , wherein the peptide is located at the amino acid positions corresponding to amino acids 451-458 of the native AAV9 capsid, or the equivalent amino acid residues in AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV10, AAV11, AAV12, AAVrh.8, AAVrh.10, AAVrh32.33, AAVrh74, bovine AAV or avian AAV, and wherein the peptide is selected from any one of SEQ ID NO: 12-18.

8 . The AAV vector of any one of claims 1 - 6 , wherein the peptide is located at the amino acid positions corresponding to amino acids 587-594 of the native AAV9 capsid, or the equivalent amino acid residues in AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV10, AAV11, AAV12, AAVrh.8, AAVrh.10, AAVrh32.33, AAVrh74, bovine AAV or avian AAV, and wherein the peptide is selected from SEQ ID NO: 19 or 20.

9 . The AAV vector of claim 1 , wherein the recombinant capsid protein comprises:

a) a first peptide having a sequence of any one of SEQ ID NO: 12-18; and

b) a second peptide having a sequence of any one of SEQ ID NO: 19-20.

10 . The AAV vector of claim 9 , wherein the first peptide is at amino acid positions 451-458, and the second peptide is at amino acids 587-594, wherein the amino acid numbering is based on the native AAV9 capsid, or the equivalent amino acid residues in AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV10, AAV11, AAV12, AAVrh.8, AAVrh.10, AAVrh32.33, AAVrh74, bovine AAV or avian AAV.

11 . The AAV vector of any one of claims 1 - 10 , wherein the peptide inhibits binding of at least one antibody to the capsid protein.

12 . The AAV vector of claim 11 , wherein the peptide inhibits neutralization of infectivity of the AAV vector by the antibody.

13 . The AAV vector of any one of claims 1 - 12 , wherein the peptide selectively binds to a receptor expressed on the surface of a cell in the central nervous system (CNS).

14 . The AAV vector of claim 13 , wherein the cell is in the premotor cortex, the thalamus, the cerebellar cortex, the dentate nucleus, the spinal cord, or the dorsal root ganglion.

15 . The AAV vector of any one of claims 1 - 14 , wherein the peptide selectively binds to a receptor expressed on the surface of a cell in the heart.

16 . The AAV vector of any one of claims 1 - 15 , wherein the capsid protein further comprises a peptide that modifies the HI loop of the capsid.

17 . An adeno-associated virus (AAV) vector comprising (i) a mutant AAV9 capsid protein and (ii) a cargo nucleic acid encapsidated by the capsid protein, wherein the capsid protein comprises a peptide having the sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 (SEQ ID NO: 158) at amino acids 451-458 of the native AAV9 capsid protein sequence, wherein the peptide does not occur in the native AAV9 capsid protein sequence.

18 . The AAV vector of claim 17 , wherein X 1 is not I, X 2 is not N, X 3 is not G, X 4 is not S, X 5 is not G, X 6 is not Q, X 7 is not N, and/or X 8 is not Q.

19 . The AAV vector of claim 18 , wherein X 1 is S, F, Q, G, K, or R.

20 . The AAV vector of claim 18 or 19 , wherein X 2 is C, G, R, D, T, or Q.

21 . The AAV vector of any one of claims 18 - 20 , wherein X 3 is Q, V, G, Y, R, F, or D.

22 . The AAV vector of any one of claims 18 - 21 , wherein X 4 is P, Q, A, or R.

23 . The AAV vector of any one of claims 18 - 22 , wherein X 5 is T, N, A, P, or I.

24 . The AAV vector of anyone of claims 18 - 23 , wherein X 6 is V, Q, A, or I.

25 . The AAV vector of any one of claims 18 - 24 , wherein X 7 is M, P, R, Q, or N.

26 . The AAV vector of any one of claims 18 - 25 , wherein X 8 is N, L, F, E, H, or A.

27 . The AAV vector of claim 17 , wherein X 1 is S, X 2 is C, X 3 is Q, X 4 is P, X 5 is T, X 6 is V, X 7 is M, and X 8 is N.

28 . The AAV vector of claim 17 , wherein X 1 is F, X 2 is G, X 3 is V, X 4 is P, X 5 is N, X 6 is Q, X 7 is P, and X 8 is L.

29 . The AAV vector of claim 17 , wherein X 1 is Q, X 2 is R, X 3 is G, X 4 is Q, X 5 is A, X 6 is A, X 7 is P, and X 8 is F.

30 . The AAV vector of claim 17 , wherein X 1 is G, X 2 is D, X 3 is Y, X 4 is A, X 5 is P, X 6 is I, X 7 is R, and X 8 is E.

31 . The AAV vector of claim 17 , wherein X 1 is K, X 2 is T, X 3 is R, X 4 is R, X 5 is I, X 6 is V, X 7 is Q, and X 8 is H.

32 . The AAV vector of claim 17 , wherein X 1 is F, X 2 is G, X 3 is F, X 4 is P, X 5 is N, X 6 is Q, X 7 is P, and X 8 is L.

33 . The AAV vector of claim 17 , wherein X 1 is R, X 2 is Q, X 3 is D, X 4 is Q, X 5 is P, X 6 is I, X 7 is N, and X 8 is A.

34 . An adeno-associated virus (AAV) vector comprising (i) a mutant AAV9 capsid protein and (ii) a cargo nucleic acid encapsidated by the capsid protein, wherein the capsid protein comprises a peptide having the sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 (SEQ ID NO: 158) at amino acids 587-594 of the native AAV9 capsid protein sequence, wherein the peptide does not occur in the native AAV9 capsid protein sequence.

35 . The AAV vector of claim 34 , wherein X 1 is not A, X 2 is not Q, X 3 is not A, X 4 is not Q, X 5 is not A, X 6 is not Q, X 7 is not T, and/or X 8 is not G.

36 . The AAV vector of claim 35 , wherein X 1 is S.

37 . The AAV vector of claim 35 or 36 , wherein X 2 is K or T.

38 . The AAV vector of any one of claims 35 - 37 , wherein X 3 is V.

39 . The AAV vector of any one of claims 35 - 38 , wherein X 4 is E or D.

40 . The AAV vector of any one of claims 35 - 39 , wherein X 5 is S.

41 . The AAV vector of any one of claims 35 - 40 , wherein X 6 is W or I.

42 . The AAV vector of any one of claims 35 - 41 , wherein X 7 is T or A.

43 . The AAV vector of any one of claims 35 - 42 , wherein X 8 is E or I.

44 . The AAV vector of claim 34 , wherein X 1 is S, X 2 is K, X 3 is V, X 4 is E, X 5 is S, X 6 is W, X 7 is T, and X 8 is E.

45 . The AAV vector of claim 34 , wherein X 1 is S, X 2 is T, X 3 is V, X 4 is D, X 5 is S, X 6 is I, X 7 is A, and X 8 is I.

46 . An adeno-associated virus (AAV) vector comprising (i) a recombinant capsid protein and (ii) a cargo nucleic acid encapsidated by the capsid protein, wherein the capsid protein comprises an amino acid sequence that is at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to any one of SEQ ID NO: 165-187.

47 . The AAV vector of claim 46 , wherein the capsid protein comprises the amino acid sequence of any one of SEQ ID NO: 165-187.

48 . The AAV vector of claim 47 , wherein the capsid protein comprises the amino acid sequence of SEQ ID NO: 175.

49 . The AAV vector of claim 47 , wherein the capsid protein comprises the amino acid sequence of SEQ ID NO: 180.

50 . The AAV vector of any one of claims 46 - 49 , wherein the AAV vector selectively delivers the cargo nucleic acid to a cell or tissue of the central nervous system.

51 . The AAV vector of claim 50 , wherein the tissue of the central nervous system is the premotor cortex, the thalamus, the cerebellar cortex, the dentate nucleus, the spinal cord, or the dorsal root ganglion.

52 . The AAV vector of any one of claims 46 - 49 , wherein the AAV vector delivers the cargo nucleic acid to the brain, but does not deliver the AAV vector to the heart.

53 . The AAV vector of any one of claims 46 - 49 , wherein the AAV vector delivers the cargo nucleic acid to the brain and to the heart.

54 . The AAV vector of claim 53 , wherein delivery of the cargo nucleic acid is greater to the brain than to the heart.

55 . The AAV vector of claim 53 , wherein delivery of the cargo nucleic acid is approximately equal in the brain in the heart.

56 . A nucleic acid sequence encoding the recombinant capsid protein of the AAV vector of any one of claims 1 to 55 .

57 . The nucleic acid sequence of claim 56 , wherein the nucleic acid sequence is a DNA sequence.

58 . The nucleic acid sequence of claim 56 , wherein the nucleic acid sequence is an RNA sequence.

59 . An expression vector comprising the nucleic acid sequence of any one of claims 56 - 58 .

60 . A cell comprising the nucleic acid sequence of any one of claims 56 - 58 .

61 . A cell comprising the expression vector of claim 59 .

62 . A pharmaceutical composition comprising the AAV vector of any one of claims 1 - 55 .

63 . The pharmaceutical composition of claim 62 , wherein the composition further comprises a pharmaceutically acceptable carrier.

64 . A pharmaceutical composition comprising the cell of claim 60 or 61 .

65 . The pharmaceutical composition of claim 64 , wherein the composition further comprises a pharmaceutically acceptable carrier.

66 . A method of treating a subject in need thereof comprising administering to the subject a therapeutically effective amount of the AAV vector of any one of claims 1 - 55 .

67 . The method of claim 66 , wherein the subject has a disease or disorder of the central nervous system.

68 . The method of claim 66 or 67 , wherein the subject is a mammal.

69 . The method of claim 68 , wherein the subject is a human.

70 . An in vitro method of introducing a nucleic acid molecule into a cell, comprising contacting the cell with the AAV vector of any one of claims 1 - 55 .

71 . An AAV vector of any one of claims 1 - 55 for use as a medicament.

72 . An AAV vector of any one of claims 1 - 55 for use in a method of treatment of a subject in need thereof.

73 . An AAV vector of any one of claims 1 - 55 for use in a method of treating or preventing a disease or disorder of the CNS in a subject in need thereof.