AAV2-CMV-iCre

Of the 12 different AAV serotypes identified to date, adeno-associated virus type 2 (AAV2) is the most extensively studied. Recombinant vectors based on AAV2 have been widely used for gene therapy applications in animal models and human clinical trials. Conventional AAV vectors carry a linear single-stranded DNA genome containing the therapeutic transgene and a promoter, flanked by palindromic inverted terminal repeats. The 60-subunit icosahedral AAV2 capsid is assembled from three overlapping viral proteins, VP1 (87 kd), VP2 (73 kd), and VP3 (62 kd), encoded by the cap gene, in a predicted ratio of 1:1:10. The three VP capsid proteins share a common C-terminal sequence, with VP1 containing a unique 138 amino acid N-terminal region (VP1u). VP3 is the most abundant AAV2 capsid protein, accounting for approximately 90% of its structure.

Heparan sulfate proteoglycans on the cell surface are the major viral receptors for AAV serotype 2. Several positively charged residues of AAV2, including R484, R487, K527, K532, R585, and R588, have been implicated in heparin binding. In addition, coreceptors such as human fibroblast growth factor receptor 1, integrins αvβ5 and α5β1, 37/67 kd laminin receptor, and hepatocyte growth factor receptor are also thought to interact with AAV2 on the cell surface and regulate internalization and transduction efficiency.