AAV2-hSyn-NULL

AAVs have shown great potential as gene delivery vectors for the correction of single gene defects. They have the following advantages: they do not cause disease, have a stable virus particle that can be purified by biomedically accepted methods used for recombinant protein products, can be produced void of viral coding genes, can transduce dividing and nondividing cells, and can induce long-term transgene expression in certain cell types.

To date, most gene therapy applications have used AAV2, including the treatment of blindness in patients with Leber congenital amaurosis. There is growing interest in using other serotypes (e.g., AAV1, AAV5, AAV6, and AAV8) because of their different tissue specificity, cell transduction efficiency, and antigenicity. AAV2 has also received the most attention in dissecting the mechanisms of cell entry and trafficking. For this serotype, attachment to the host cell surface is mediated by heparin sulfate proteoglycans (HSPGs). Several secondary or coreceptors have been reported to mediate entry through dynein-dependent clathrin-mediated endocytosis. AAV2 may also enter cells through dynein- and clathrin-independent pathways. HSPGs have been found to bind to AAV3 strains B and H, with strain H receptor binding extending to fibroblast growth factor receptor-1.