AAV2-Syn-iCre

Adeno-associated virus (AAV) is a nonenveloped, single-stranded DNA virus of the genus Dependoparvovirus in the family Parvoviridae. Unlike most viruses, AAV is inherently nonpathogenic, poorly immunogenic, and has broad tropism, making it an attractive candidate for gene delivery for viral-based gene therapies. Most naturally occurring AAVs utilize glycan moieties for initial attachment to the cell surface, and these interactions have been well characterized across multiple serotypes. To date, interacting glycan moieties identified include heparin sulfate proteoglycans for AAV serotypes 2 (AAV2), AAV3, and AAV6; N-terminal galactose for AAV9; and specific N- or O-linked sialic acid moieties for AAV1, -4, -5, and -6. Following attachment, AAV is thought to bind to protein receptors to mediate cell entry. For AAV2, the most intensively studied AAV serotype, several studies have investigated possible cellular receptors. The characterization of a putative AAV2 receptor was first reported by Mizukami et al., describing a 150 kDa glycoprotein detected in the membrane fraction of AAV-permissive cells that bound to AAV2 particles in a viral overlay assay. Since then, several protein coreceptors, such as fibroblast growth factor receptor 1 (FGFR-1), integrin αVβ5, and hepatocyte growth factor receptor (c-Met), have been implicated in AAV2 entry. However, clustered regularly interspaced short palindromic repeats (CRISPR)-mediated knockout of FGFR-1 and c-Met had no significant effect on AAV2 transduction in several cell lines, suggesting that these coreceptors play an auxiliary, rather than essential, role in AAV2 transduction.