AAV CAPSID DESIGNS
The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associated viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.
1 . A recombinant expression vector comprising a nucleic acid encoding a polypeptide having a sequence selected from the group consisting of: SEQ ID NOs: 21-62, 67-799, 802-1725, and 1729-1986.
2 . An isolated AAV capsid protein comprising an amino acid sequence selected from the group consisting of: SEQ ID NOs: 21-62, 67-799, 802-1725, and 1729-1986.
3 .- 7 . (canceled)
8 . An recombinant expression vector comprising a nucleic acid sequence encoding the isolated AAV capsid protein of claim 2 .
9 .- 10 . (canceled)
11 . A recombinant AAV (rAAV) comprising the isolated AAV capsid protein of claim 2 .
12 .- 13 . (canceled)
14 . A host cell containing a recombinant expression vector of claim 8 .
15 .- 17 . (canceled)
17 . A method for delivering at least one transgene to a subject comprising administering a rAAV of claim 11 to a subject, wherein the rAAV comprises the at least one transgene, and wherein the rAAV infects cells of a target tissue of the subject.
18 . A method for generating a somatic transgenic animal model comprising administering a recombinant rAAV of claim 11 to a non-human animal, wherein the rAAV comprises at least one transgene, and wherein the rAAV infects cells of a target tissue of the non-human animal.
19 . The method of claim 17 , wherein the at least one transgene is a protein coding gene or encodes a small interfering nucleic acid.
20 .- 23 . (canceled)
24 . The method of claim 17 , wherein the target tissue is liver, central nervous system (CNS), bone, cartilage, ocular, gastrointestinal, respiratory, breast, pancreas, urinary tract, or uterine tissue.
25 .- 28 . (canceled)
29 . The method of claim 17 , wherein the rAAV is administered intravenously, transdermally, intraocularly, intrathecally, orally, intramuscularly, subcutaneously, intranasally, or by inhalation.
30 . The method of claim 17 , wherein the subject is selected from a human, a mouse, a rat, a rabbit, a dog, a cat, a sheep, a pig, and a non-human primate.
31 .- 35 . (canceled)
36 . A kit comprising:
a container housing a recombinant AAV having an isolated AAV capsid protein of claim 2 .
37 . (canceled)
38 . The isolated AAV capsid protein of claim 2 , wherein the capsid protein is a VP1 capsid protein, a VP2 capsid protein, or a VP3 capsid protein.
39 .- 41 . (canceled)
42 . The recombinant expression vector of claim 1 , wherein the nucleic acid encodes a V1 capsid protein, a VP2 capsid protein, or a VP3 capsid protein.
43 .- 50 . (canceled)
51 . The recombinant expression vector of claim 1 comprising a nucleic acid encoding a polypeptide having a sequence selected from the group consisting of: SEQ ID NOs: 124, 149, 161, 175, and 358.
52 . The recombinant expression vector of claim 1 comprising a nucleic acid encoding a polypeptide having a sequence selected from the group consisting of: SEQ ID NOs: 149, 152, 157, and 182.
53 . The recombinant expression vector of claim 1 comprising a nucleic acid encoding a polypeptide having a sequence selected from the group consisting of: SEQ ID NOs: 46, 56, 67, 81, 224, 326, and 358.
54 . The isolated AAV capsid protein of claim 2 comprising a nucleic acid encoding a polypeptide having a sequence selected from the group consisting of: SEQ ID NOs: 124, 149, 161, 175, and 358.
55 . The isolated AAV capsid protein of claim 2 comprising a nucleic acid encoding a polypeptide having a sequence selected from the group consisting of: SEQ ID NOs: 149, 152, 157, and 182.
56 . The isolated AAV capsid protein of claim 2 comprising a nucleic acid encoding a polypeptide having a sequence selected from the group consisting of: SEQ ID NOs: 46, 56, 67, 81, 224, 326, and 358.