Recombinant AAV variants and uses thereof
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 adeno-associated viral particle comprising an adeno-associated virus capsid and at least one heterologous transgene, wherein the adeno-associated virus capsid comprises a protein comprising an amino acid sequence selected from any one of SEQ ID NOs: 54 to 61.
2. A composition comprising the rAAV of claim 1 and a pharmaceutically acceptable carrier.
3. A method for delivering a transgene to a subject comprising administering the recombinant adeno-associated viral particle of claim 1 to a subject, wherein the recombinant adeno-associated viral particle comprises the at least one heterologous transgene, and wherein the recombinant adeno-associated viral particle infects cells of a target tissue of the subject.
4. A method for generating a somatic transgenic non-human animal model comprising administering the recombinant adeno-associated viral particle of claim 1 to a non-human animal, wherein the recombinant adeno-associated viral particle comprises the at least one heterologous transgene, and wherein the recombinant adeno-associated viral particle infects cells of a target tissue of the non-human animal.
5. The method of claim 3 , wherein the at least one heterologous transgene is a protein coding gene or encodes a small interfering nucleic acid.
6. The method of claim 5 , wherein the small interfering nucleic acid is a miRNA or a shRNA.
7. The method of claim of claim 3 , wherein the target tissue is skeletal muscle, heart, liver, pancreas, brain or lung.
8. The method of claim 3 , wherein the recombinant adeno-associated viral particle is administered intravenously, transdermally, intraocularly, intrathecally, orally, intramuscularly, subcutaneously, intranasally, or by inhalation.
9. The method of claim 3 , wherein the subject is selected from a mouse, a rat, a rabbit, a dog, a cat, a sheep, a pig, a non-human primate, or a human.
10. A somatic transgenic non-human animal model produced by the method of claim 4 .
11. A kit comprising a container housing the recombinant adeno-associated viral particle of claim 1 , wherein the container is a syringe.