Methods of predicting ancestral virus sequences and uses thereof
Methods are described for predicting ancestral sequences for viruses or portions thereof. Also described are predicted ancestral sequences for adeno-associated virus (AAV) capsid polypeptides. The disclosure also provides methods of gene transfer and methods of vaccinating subjects by administering a target antigen operably linked to the AAV capsid polypeptides.
1. A method comprising:
administering a plurality of recombinant adeno-associated virus (rAAV) particles to a subject in need thereof,
wherein each rAAV particle comprises (i) a transgene and (ii) one or more AAV capsid polypeptides that comprise an amino acid sequence according to SEQ ID NOs: 19, 20, 21, 22, 23, 24, 25, or 26, and
wherein the transgene is within the rAAV particle.
2. The method of claim 1 , wherein the one or more AAV capsid polypeptides comprises the amino acid sequence of SEQ ID NO: 19.
3. The method of claim 1 , wherein the one or more AAV capsid polypeptides comprises the amino acid sequence of SEQ ID NO: 20.
4. The method of claim 1 , wherein the one or more AAV capsid polypeptides comprises the amino acid sequence of SEQ ID NO: 21.
5. The method of claim 1 , wherein the one or more AAV capsid polypeptides comprises the amino acid sequence of SEQ ID NO: 22.
6. The method of claim 1 , wherein the one or more AAV capsid polypeptides comprises the amino acid sequence of SEQ ID NO: 23.
7. The method of claim 1 , wherein the one or more AAV capsid polypeptides comprises the amino acid sequence of SEQ ID NO: 24.
8. The method of claim 1 , wherein the one or more AAV capsid polypeptides comprises the amino acid sequence of SEQ ID NO: 25.
9. The method of claim 1 , wherein the one or more AAV capsid polypeptides comprises the amino acid sequence of SEQ ID NO: 26.
10. The method of claim 1 , wherein the method is a method of vaccinating the subject.
11. The method of claim 1 , wherein the method is a method of delivering gene therapy to the subject.
12. The method of claim 1 , wherein the subject is a human.
13. The method of claim 1 , wherein the plurality of rAAV particles are administered in a composition comprising a pharmaceutically acceptable carrier.
14. The method of claim 1 , wherein the plurality of rAAV particles transduces or infects cells in the subject.
15. The method of claim 14 , wherein the cells are ear cells.
16. The method of claim 15 , wherein the ear cells are inner ear cells.
17. The method of claim 1 , wherein a therapeutically effective dose of the rAAV particles is administered.
18. A method of vaccinating or delivering gene therapy to a subject, the method comprising:
administering a therapeutically effective dose of recombinant adeno-associated virus (rAAV) particles to a subject,
wherein each rAAV particle comprises (i) a transgene and (ii) one or more AAV capsid polypeptides that comprise an amino acid sequence according to SEQ ID NOs: 19, 20, 21, 22, 23, 24, 25, or 26, and
wherein the transgene is within the rAAV particle.
19. The method of claim 18 , wherein the rAAV particles transduce or infect cells in the subject.
20. A method of delivering a transgene to a subject, the method comprising:
obtaining recombinant adeno-associated virus (rAAV) particles, wherein each rAAV particle comprises (i) one or more AAV capsid polypeptides and (ii) a transgene located within the rAAV particle, wherein the one or more AAV capsid polypeptides comprise an amino acid sequence according to SEQ ID NO: 19, 20, 21, 22, 23, 24, 25, or 26; and
administering to the subject in need thereof a therapeutically effective amount of the rAAV particles.
21. The method of claim 20 , wherein obtaining the one or more rAAV particles comprises purifying.