Variant adeno-associated viruses and methods of using
The present disclosure provides AAV variants that exhibit a preference for retrograde movement in neurons and methods of using such variants.
1. A viral capsid protein, wherein the viral capsid protein comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 8, 10, 12, 14, 18, 22, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 54, 56, 60, 64, 66, 68, 70, 72, 74, 76, and 78.
2. A viral particle comprising the viral capsid protein of claim 1 .
3. The viral particle of claim 2 , wherein the viral particle exhibits enhanced retrograde movement compared to a wild type viral particle.
4. The viral particle of claim 2 , wherein the viral particle possesses retrograde transport capability.
5. The viral particle of claim 2 , wherein the viral particle exhibits up to two orders of magnitude greater retrograde access to cortico-pontine projection neurons than canine adenovirus-2 (CAV-2).
6. The viral particle of claim 5 , wherein the retrograde access to cortico-pontine projection neurons or afferents to the dorsomedial striatum (DMS) is comparable to a synthetic retrograde labeling reagent.
7. A method of delivering a payload to one or more neurons, the method comprising:
contacting one or more neurons with a variant adeno-associated virus (AAV) comprising a payload packaged therein, wherein the variant AAV comprises a capsid protein comprising a sequence selected from the group consisting of SEQ ID NO:6, 8, 10, 12, 14, 18, 22, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 54, 56, 60, 64, 66, 68, 70, 72, 74, 76, and 78.
8. The method of claim 7 , wherein the variant AAV exhibits retrograde movement in the neurons.
9. The method of claim 7 , wherein the neurons are projection neurons.
10. The method of claim 7 , wherein the neurons are in a subject.
11. The method of claim 7 , wherein the neurons are in the central nervous system (CNS) in a subject.
12. The method of claim 10 , wherein the subject is a human.
13. The method of claim 10 , wherein the subject is a non-human.
14. The method of claim 13 , wherein the non-human subject is a primate, a rodent, a reptile, and a bird.
15. The method of claim 7 , wherein the contacting step is in cell culture.
16. The method of claim 7 , wherein the contacting step is in vivo via intracranial, intraspinal or intramuscular injection.
17. The viral capsid protein of claim 1 , wherein the viral capsid protein comprises the amino acid sequence SEQ ID NO:44.
18. The method of claim 7 , wherein the viral capsid protein comprises the amino acid sequence SEQ ID NO:44.