| 摘要 |
Disclosed are capsid-modified rAAV particles and expression vectors, as well as compositions and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and using novel capsid-protein-mutated particle or rAAV vector constructs in a variety of diagnostic and therapeutic applications including, inter alia, as delivery agents for diagnosis, treatment, or amelioration of one or more diseases, disorders, or dysfunctions of the mammalian eye. Also disclosed are methods for subretinal delivery of therapeutic gene constructs to mammalian photoreceptors and retinal pigment epithelial cells, as well as use of the disclosed compositions in the manufacture of medicaments for a variety of in vitro and/or in vivo applications including the treatment of a variety of inherited retinal diseases. |
| 主权项 |
1. A recombinant adeno-associated viral (rAAV) particle comprising:
a modified capsid protein, wherein the modified capsid protein comprises one or more non-native amino acid substitutions at positions corresponding to one or more heparin-sulfate-binding surface-exposed amino acid residues of a wild-type AAV2 capsid protein as set forth in SEQ ID NO:2; or to amino acid residues corresponding thereto in any one of the wild-type AAV1, AAV3, AAV4, AAV5, AAV6, AAV7, AAV9, or AAV10 capsid proteins, as set forth, respectively, in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, or SEQ ID NO:10. |
