Aav9 capsid variants escaping neutralizing human antibodies
AssigneeUniversity of Florida Research Foundation, Inc.
InventorsRobert McKenna, Mario Mietzsch, Jane Hsi, Austin Nelson
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Abstract
This disclosure relates to variant AAV9 particles engineered to escape host neutralizing antibodies but retain or improve transduction efficiency, production efficiency and/or infectivity, and their use as gene delivery vehicles.
Claims105
A recombinant adeno-associated virus 9 (rAAV9) particle comprising a capsid protein comprising one or more mutations, wherein said mutations result in modulated reactivity to a neutralizing antibody, altered or unchanged production efficiency, and/or altered or unchanged infectivity, relative to a wild-type AAV9 particle having a capsid protein with an amino acid sequence of SEQ ID NO:
- 2.
The rAAV9 particle of any of the preceding claims, wherein:
- (a) the reactivity to neutralizing antibodies is decreased;
- and/or
- (b) the production efficiency is:
- (i) unchanged, or
- (ii) increased;
- and/or
- (c) the infectivity is:
- (i) unchanged, or
- (ii) increased.
The rAAV9 particle of any one of the preceding claims, wherein the capsid protein is one or more of the capsid proteins selected from the group consisting of:
- VP1, VP2 and VP3.
The rAAV9 particle of any one of the preceding claims, wherein the one or more mutations comprise an amino acid substitution or an amino acid deletion.
The rAAV9 particle of any one of the preceding claims, wherein the one or more mutations are at amino acid positions selected from the group consisting of:
- D327, N329, D441, T491, V493, R533, N552, V553, D556, 1560, N562, Q588, W595, Q597, A656, P658, Y706, and N709.
The rAAV9 particle of any one of the preceding claims, wherein the one or more mutations are amino acid substitution(s) selected from the group consisting of:
- D327R, D327T, N329D, D441N, T491R, V493P, R533S, N552A, V553A, D556P, 1560F, N562Y, Q588R, W595G, Q597S, A656G, P658L, Y706D, N709I, and N709Y.
The rAAV9 particle of any one of the preceding claims, further comprising a transgene comprising a gene of interest.
A composition comprising a rAAV9 particle of any one of the preceding claims.
A capsid protein of serotype AAV9 comprising a mutation in the D327 amino acid position in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising a mutation in the D441 amino acid position in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising a mutation in the T491 amino acid position in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising a mutation in the V493 amino acid position in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising a mutation in the R533 amino acid position in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising a mutation in the N552 amino acid position in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising a mutation in the V553 amino acid position in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising a mutation in the D556 amino acid position in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising a mutation in the I560 amino acid position in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising a mutation in the N562 amino acid position in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising a mutation in the Q588 amino acid position in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising a mutation in the Y706 amino acid position in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising a mutation in the N709 amino acid position in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising one or more mutations in amino acid positions selected from the group consisting of:
- D327 and N329 in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising one or more mutations in amino acid positions selected from the group consisting of:
- N552 and V553 in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising one or more mutations in amino acid positions selected from the group consisting of:
- W595 and Q597 in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising one or more mutations in amino acid positions selected from the group consisting of:
- A656 and P658 in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising one or more mutations in amino acid positions selected from the group consisting of:
- Y706 and N709 in SEQ ID NO:
- 2.
A capsid protein of serotype AAV9 comprising one or more mutations in amino acid positions selected from the group consisting of:
- Q588 and T491 in SEQ ID NO:
- 2.
Dependencies are inferred from the claim text.