Granted Patent
B2
US 12,227,543 · App. 16/989,454 · Granted Feb 18, 2025
Ancestral virus sequences and uses thereof
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Abstract
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.
Claims (25)
1. An adeno-associated virus (AAV) capsid polypeptide having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 58.
2. The AAV capsid polypeptide of claim 1 , wherein the polypeptide has 100% sequence identity to the amino acid sequence of SEQ ID NO: 58.
3. The AAV capsid polypeptide of claim 1 , wherein the AAV capsid polypeptide is purified.
4. A nucleic acid molecule having at least 98% sequence identity to a nucleic acid molecule encoding an adeno-associated virus (AAV) capsid polypeptide having the amino acid sequence of SEQ ID NO:58.
5. The nucleic acid molecule of claim 4 , having at least 99% sequence identity to the nucleic acid molecule encoding the AAV capsid polypeptide having the amino acid sequence of SEQ ID NO:58.
6. The nucleic acid molecule of claim 5 , having 100% identity to the nucleic acid molecule encoding the AAV capsid polypeptide having the amino acid sequence of SEQ ID NO:58.
7. A vector comprising the nucleic acid molecule of claim 4 .
8. An isolated host cell comprising the vector of claim 7 .
9. A virus particle comprising the AAV capsid polypeptide of claim 1 .
10. The virus particle of claim 9 , further comprising a transgene.
11. A method of gene transfer or vaccination with a transgene, the method comprising administering a virus particle to a subject in need of gene transfer or vaccination, wherein the virus particle comprises an adeno-associated virus (AAV) capsid polypeptide having the amino acid sequence of SEQ ID NO:58 and further comprises a transgene.
12. A method of vaccinating a subject, the method comprising administering a target antigen linked to an adeno-associated virus (AAV) capsid polypeptide having the amino acid sequence of SEQ ID NO:58 to a subject in need of vaccination.
13. An adeno-associated virus (AAV) capsid polypeptide having the amino acid sequence of SEQ ID NO:58 or a variant thereof, wherein the variant has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:58 and has at least one amino acid substitution selected from Ser157Thr, Lys168Arg, Ala456Gly, Gln462Ala, Thr507Ala, Tyr509Phe, His510Lys, Gln557Asn, Asn584His, and Ser586Ala relative to SEQ ID NO:58.
14. The AAV capsid polypeptide of claim 13 , wherein the variant has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:58 and has at least four amino acid substitutions selected from Ser157Thr, Lys168Arg, Ala456Gly, Gln462Ala, Thr507Ala, Tyr509Phe, His510Lys, Gln557Asn, Asn584His, and Ser586Ala relative to SEQ ID NO:58.
15. The AAV capsid polypeptide of claim 13 , wherein the variant has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:58 and has at least five amino acid substitutions selected from Ser157Thr, Lys168Arg, Ala456Gly, Gln462Ala, Thr507Ala, Tyr509Phe, His510Lys, Gln557Asn, Asn584His, and Ser586Ala relative to SEQ ID NO:58.
16. The AAV capsid polypeptide of claim 13 , wherein the variant has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:58 and has at least six amino acid substitutions selected from Ser157Thr, Lys168Arg, Ala456Gly, Gln462Ala, Thr507Ala, Tyr509Phe, His510Lys, Gln557Asn, Asn584His, and Ser586Ala relative to SEQ ID NO:58.
17. The AAV capsid polypeptide of claim 13 , wherein the variant has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:58 and has at least seven amino acid substitutions selected from Ser157Thr, Lys168Arg, Ala456Gly, Gln462Ala, Thr507Ala, Tyr509Phe, His510Lys, Gln557Asn, Asn584His, and Ser586Ala relative to SEQ ID NO:58.
18. The AAV capsid polypeptide of claim 13 , wherein the variant has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:58 and has at least eight amino acid substitutions selected from Ser157Thr, Lys168Arg, Ala456Gly, Gln462Ala, Thr507Ala, Tyr509Phe, His510Lys, Gln557Asn, Asn584His, and Ser586Ala relative to SEQ ID NO:58.
19. The AAV capsid polypeptide of claim 13 , wherein the variant has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:58 and has at least nine amino acid substitutions selected from Ser157Thr, Lys168Arg, Ala456Gly, Gln462Ala, Thr507Ala, Tyr509Phe, His510Lys, Gln557Asn, Asn584His, and Ser586Ala relative to SEQ ID NO:58.
20. The AAV capsid polypeptide of claim 13 , wherein the AAV capsid polypeptide is purified.
21. A nucleic acid molecule encoding the AAV capsid polypeptide of claim 13 .
22. A vector comprising a nucleic acid molecule encoding the AAV capsid polypeptide of claim 13 .
23. An isolated host cell comprising a nucleic acid molecule encoding the AAV capsid polypeptide of claim 13 .
24. A purified virus particle comprising the AAV capsid polypeptide of claim 13 .
25. A pharmaceutical composition comprising a purified virus particle comprising the AAV capsid polypeptide of claim 13 in a pharmaceutically acceptable excipient.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 17, 2020
From: ZINN, ERIC
To: SCHEPENS EYE RESEARCH INSTITUTE
Reel/Frame 053507/0901 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 17, 2020
From: VANDENBERGHE, LUK H.
To: MASSACHUSETTS EYE AND EAR INFIRMARY
Reel/Frame 053507/0916 →
Continuity (4)
Continuation
15748738
Provisional Application
62203002
· Aug 10, 2015
Provisional Application
62199059
· Jul 30, 2015
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