Modified AAV capsid proteins and uses thereof
AssigneesUniversity of Florida Research Foundation, Inc., The UAB Research Foundation
InventorsSergei Zolotukhin, Sanford L. Boye, Shannon E. Boye, Damien Marsic, Paul D. Gamlin
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Abstract
Adeno associated viral (AAV) particles are emerging as a useful vehicle for gene delivery to various organs and tissues, one of them being the retina. Provided here are variant AAV (for example, variant serotype 2 (AAV2)) capsid proteins and variant capsid protein containing particles with enhanced ability to transduce retinal cells.
Claims19
A variant recombinant adeno-associated virus (rAAV) capsid protein comprising a peptide inserted into the capsid protein between positions 585 and 588 of AAV2 VP1 capsid protein and comprising any one of the following combinations of amino acid substitutions selected from:
- a) aspartic acid, glycine, glutamic acid, aspartic acid, phenylalanine, at positions corresponding to amino acids 492, 493, 494, 499 and 500 of AAV2 VP1 capsid protein, respectively;
- b) asparagine, alanine, aspartic acid, glycine, glutamic acid, aspartic acid, and phenylalanine at positions corresponding to amino acids 263, 264, 492, 493, 494, 499, and 500 of AAV2 VP1 capsid protein, respectively, and SAAGADXAXDS (SEQ ID NO:
- 5) at positions corresponding to amino acids 546-556 of AAV2 VP1 capsid protein, wherein X is any amino acid;
- c) alanine, threonine, proline, aspartic acid, phenylalanine, and aspartic acid at positions corresponding to amino acids 263, 490, 492, 499, 500, and 530 of AAV2 VP1 capsid protein, respectively;
- d) asparagine, alanine, phenylalanine, alanine, asparagine, valine, threonine, arginine, aspartic acid, and aspartic acid at positions corresponding to amino acids 263, 264, 444, 451, 454, 455, 459, 527, 530, and 531 of AAV2 VP1 capsid protein, respectively;
- and
- e) aspartic acid, glycine, glutamic acid, aspartic acid, and phenylalanine at positions corresponding to amino acids 492, 493, 494, 499, and 500 of AAV2 VP1 capsid protein, respectively, and EDATENXIXXDR (SEQ ID NO:
- 4) at positions corresponding to amino acids 545-556 of AAV2 VP1 capsid protein, wherein X is any amino acid.
A variant rAAV capsid protein of a serotype other than serotype 2 comprising any one of the combinations of amino acid substitutions in accordance with claim/3, wherein the substitutions are at positions homologous to the amino acids of a wild-type AAV2 VP1 capsid sequence as set forth in SEQ ID NO:
- 1.
Dependencies are inferred from the claim text.