Adeno-associated virus type 2 capsid protein-replication protein interface (AAV2 VP-Rep interface)

The Adeno-associated virus type 2 (AAV2) capsid protein-replication protein interface is a critical macromolecular interaction site responsible for the encapsidation of the viral genome. This interface involves the structural VP proteins (VP1, VP2, and VP3) that form the icosahedral capsid and the non-structural Rep proteins, specifically the smaller variants Rep52 and Rep40, which function as ATP-dependent DNA helicases (King et al., 2001, J. Virol.). During the viral life cycle, Rep proteins bind to the pre-formed empty capsid and translocate the single-stranded DNA genome into the interior through a portal at the five-fold symmetry axis (Bleker et al., 2006, J. Virol.). In the field of biotechnology, this interface is a primary focus for optimizing gene therapy vector production, as the efficiency of this interaction directly determines the ratio of full to empty capsids (Wistuba et al., 1997, J. Virol.). Understanding and engineering this interface allows for the development of more potent vectors with improved packaging capacity and reduced manufacturing impurities. While not a traditional target for small-molecule therapeutics, it is a vital target for synthetic biology and protein engineering to enhance the delivery of therapeutic genes (Smith et al., 2003, J. Virol.).

Other names

AAV2 VP-Rep interaction siteAAV2 capsid-Rep protein complexAAV2 genome packaging interfaceAAV2 encapsidation complex

Inhibition of viral genome encapsidation or modulation of packaging efficiency through protein engineering