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1. (WO2018064624) AAVRH.10 VARIANTS WITH HOST ANTIBODY ESCAPE CAPABILITIES AND ALTERED TISSUE TARGETING PROPERTIES
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CLAIMS

1. A recombinant adeno-associated virus rh.10 (rAAVrh.10) particle comprising a capsid protein comprising one or more mutations that result in modulated reactivity to a neutralizing antibody and/or altered transduction efficiency relative to a wild-type AAVrh.lO particle, having a capsid protein with an amino acid sequence of SEQ ID NO: 2.

2. The rAAVrh.10 particle of claim 1, wherein the neutralizing antibody is against

AAVrh. lO or AAV of another serotype.

3. The rAAVrh.10 particle of claim 2, wherein the AAV of another serotype is AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAVl l, AAV 12 or AAV13.

4. The rAAVrh.10 particle of claim 2 or 3, wherein the AAV of another serotype is AAV8.

5. The rAAVrh.10 particle of claim 1, wherein the neutralizing antibody is ADK8, ADK9, IVIG, HL2381 or HL2383.

6. The rAAVrh.10 particle of claim 5, wherein the neutralizing antibody is ADK8.

7. The rAAVrh.10 particle of claim 5, wherein the neutralizing antibody is ADK8/9.

8. The rAAVrh.10 particle of claim 5, wherein the neutralizing antibody is HL2383.

9. The rAAVrh.10 particle of any of the preceding claims, wherein the reactivity to neutralizing antibodies is decreased compared to wild type AAVrh.lO particles.

10. The rAAVrh.10 particle of claim 6, wherein the reactivity to neutralizing antibodies is decreased by 5-100% compared to wild type AAVrh. lO particles.

11. The rAAVrh.10 particle of claim 9 or 10, wherein the reactivity to neutralizing antibodies is decreased by 70-100% compared to wild type AAVrh. lO particles.

12. The rAAVrh.10 particle of any one of the preceding claims, wherein the transduction efficiency is increased compared to wild type AAVrh.lO particles.

13. The rAAVrh.10 particle of claim 12, wherein the transduction efficiency is increased by 5-200% compared to wild type AAVrh.lO particles.

14. The rAAVrh.10 particle of claim 12 or 13, wherein the transduction efficiency is increased by 5-60% compared to wild type AAVrh. lO particles.

15. The rAAVrh.10 particle of any one of the preceding claims, wherein the transduction efficiency is decreased compared to wild type AAVrh. lO particles.

16. The rAAVrh.10 particle of claim 15, wherein the transduction efficiency is decreased by 5-100% compared to wild type AAVrh.lO particles.

17. The rAAVrh.10 particle of claim 15 or 16, wherein the transduction efficiency is decreased by 20-70% compared to wild type AAVrh. lO particles.

18. The rAAVrh.10 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 VPl, VP2 and VP3.

19. The rAAVrh.10 particle of claim 18, wherein the one or more mutations are amino acid positions selected from the group consisting of: K259, K333, S453, S501, S559, Q589, N590, A592, S671, T674, Y708 and T719.

20. The rAAVrh.10 particle of any one of the preceding claims, wherein the one or more mutations comprise an amino acid substitution or a deletion.

21. The rAAVrh.10 particle of claim 19, wherein the one or more mutations are selected from the group consisting of K259L, K333V, AS453, S501A, S559A, Q589N, N590S, A592Q, S671A, T674V, Y708A and T719V.

22. The rAAVrh.10 particle of claim 19, wherein the one or more mutations is K259L.

23. The rAAVrh.10 particle of claim 19, wherein the one or more mutations is AS453.

24. The rAAVrh.10 particle of claim 19, wherein the one or more mutations is S559A.

25. The rAAVrh. lO particle of claim 19, wherein the one or more mutations is S671A.

26. The rAAVrh. lO particle of claim 19, wherein the one or more mutations is T719V.

27. The rAAVrh.10 particle of claim 19, wherein the one or more mutations are N590S and A592Q.

28. The rAAVrh.10 particle of claim 19, wherein the one or more mutations are Q589N, N590S and A592Q.

29. The rAAVrh.10 particle of claim 19, wherein the one or more mutations is Y708A.

30. The rAAVrh.10 particle of claim 19, wherein the one or more mutations are AS453, S559A, Q589N, N590S, A592Q and T719V.

31. The rAAVrh.10 particle of claim 19, wherein the one or more mutations are K259L, AS453, S559A, Q589N, N590S, A592Q and T719V.

32. The rAAVrh.10 particle of claim 19, wherein the one or more mutations is K333V.

33. The rAAVrh. lO particle of claim 19, wherein the one or more mutations is S501A.

34. The rAAVrh.10 particle of claim 19, wherein the one or more mutations is T674V.

35. The rAAVrh.10 particle of any one of the preceding claims, further comprising a transgene comprises a gene of interest.

36. The rAAVrh.10 particle of claim 35, wherein the gene of interest encodes a therapeutic protein.

37. The rAAVrh.10 particle of claim 36, wherein the therapeutic protein is an antibody, a peptibody, a growth factor, a clotting factor, a hormone, a membrane protein, a cytokine, a chemokine, an activating or inhibitory peptide acting on cell surface receptors or ion channels, a cell-permeant peptide targeting intracellular processes, a thrombolytic, an enzyme, a bone

morphogenetic proteins, a nuclease or other protein used for gene editing, an Fc-fusion protein, or an anticoagulant.

38. The rAAVrh.10 particle of claim 35, wherein the gene of interest encodes a detectable molecule.

39. The rAAVrh.10 particle of claim 38, wherein the detectable molecule is a fluorescent protein, a bioluminescent protein, or a protein that provides color, or a fragment thereof.

40. A composition comprising a rAAVrh.lO particle of any one of the preceding claims.

41. The composition of claim 40, further comprising a pharmaceutically acceptable carrier.

42. A method of delivering a protein of interest to a subject, the method comprising administering to the subject a composition comprising a rAAVrh. lO particle of any one of the claims 35-39, wherein the gene of interest encodes the protein of interest.

43. A vector comprising a nucleic acid encoding Cap proteins, wherein the Cap proteins form a particle of any one of claims 1-39 when the vector is used to form capsids.

44. A kit comprising the vector of claim 43 and a vector comprising AAV helper genes, wherein the vector of 43 and the vector comprising AAV helper genes are provided in a first and second container, wherein the first and second containers are different.

45. The kit of claim 44, further comprising AAV packaging cells that are provided in a third container that is separate from the first and second containers.

46. The kit of claim 44 or 45, wherein the AAV helper genes encode El, E2, E4 and/or VA helper proteins.