Aav capsids with increased tropism to brain tissue
AssigneeVoyager Therapeutics, Inc.
InventorsMathieu E. Nonnenmacher, Jinzhao Hou, Wei Wang, Matthew Child, Shaoyong Li
Life of this patent
Estimating the term…
Abstract
The disclosure relates to compositions, methods, and processes for the preparation, use, and/or formulation of adeno-associated virus capsid proteins, wherein the capsid proteins comprise targeting peptide inserts for enhanced tropism to a target tissue.
Claims31
-51. (canceled)
An AAV capsid variant, comprising:
- (a) the amino acid sequence of any of SEQ ID NOs:
- 3648-3659 or 1725-3622;
- (b) an amino acid sequence comprising at least 5, 6, 7, 8, or 9 consecutive amino acids from the amino acid sequence of any of SEQ ID NO:
- 3648-3659 or 1725-3622;
- or
- (c) an amino acid sequence comprising at least one, two, or three but no more than four modifications, e.g., substitutions, relative to the amino acid sequence of any of 3648-3659 or 1725-3622;
- wherein the capsid variant comprises the amino acid sequence of SEQ ID NO:
- 138, or an amino acid sequence with at least 95% sequence identity thereto, and
- wherein the amino acid sequence of (a), (b), or (c) is present immediately subsequent to position 586, 588, or 589, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO:
- 138.
An AAV capsid variant, comprising:
- (i) the amino acid sequence of PLNGAVHLY (SEQ ID NO:
- 3648);
- (ii) an amino acid sequence comprising at least 5, 6, 7, 8, or 9 consecutive amino acids from the amino acid sequence of PLNGAVHLY (SEQ ID NO:
- 3648);
- or
- (iii) an amino acid sequence comprising at least one, two, or three but no more than four modifications, e.g., substitutions, relative to the amino acid sequence of PLNGAVHLY (SEQ ID NO:
- 3648);
- and
- wherein the capsid variant comprises the amino acid sequence of SEQ ID NO:
- 138, or an amino acid sequence with at least 95% sequence identity thereto.
An AAV capsid variant, comprising:
- (i) the amino acid sequence of IVMNSLK (SEQ ID NO:
- 3651);
- (ii) an amino acid sequence comprising at least 5, 6, or 7 consecutive amino acids from the amino acid sequence of IVMNSLK (SEQ ID NO:
- 3651);
- or
- (iii) an amino acid sequence comprising at least one, two, or three but no more than four modifications, e.g., substitutions, relative to the amino acid sequence of IVMNSLK (SEQ ID NO:
- 3651);
- and
- wherein the capsid variant comprises the amino acid sequence of SEQ ID NO:
- 138, or an amino acid sequence with at least 95% sequence identity thereto.
A method of delivering a payload to a cell or tissue, comprising administering an effective amount of an AAV particle comprising an AAV capsid variant and a payload, wherein the AAV capsid variant comprises:
- (a) the amino acid sequence of any of SEQ ID NO:
- 3648-3659 or 1725-3622;
- (b) an amino acid sequence comprising at least 5, 6, 7, 8, or 9 consecutive amino acids from the amino acid sequence of any of SEQ ID NO:
- 3648-3659 or 1725-3622;
- or
- (c) an amino acid sequence comprising at least one, two, or three but no more than four modifications, e.g., substitutions relative to the amino acid sequence of any of 3648-3659 or 1725-3622;
- and
- wherein the capsid variant comprises the amino acid sequence of SEQ ID NO:
- 138, or an amino acid sequence with at least 95% sequence identity thereto.
Dependencies are inferred from the claim text.