Cell surface receptors and coreceptors mediating recombinant adeno-associated virus capsid entry (rAAV receptors)

Cell surface receptors and coreceptors mediating recombinant adeno-associated virus (rAAV) capsid entry are a diverse group of molecules that determine the efficiency and specificity of gene therapy delivery. The entry process typically begins with the attachment of the AAV capsid to cell surface glycans, such as heparan sulfate proteoglycans (HSPG) for AAV2 or sialic acid for AAV1, AAV5, and AAV6 (Summerford & Samulski, 1998, J. Virol.; Wu et al., 2006, J. Virol.). Following attachment, the virus interacts with a high-affinity protein receptor, most notably the adeno-associated virus receptor (AAVR/KIAA0319L), which is essential for the internalization of most AAV serotypes (Pillay et al., 2016, Nature). Other coreceptors, including fibroblast growth factor receptor 1 (FGFR1), hepatocyte growth factor receptor (c-Met), and various integrins, further facilitate endocytosis and intracellular trafficking (Qing et al., 1999, Nat. Med.). These receptors are the primary determinants of tropism for AAV-based drugs like Onasemnogene abeparvovec and Voretigene neparvovec. Engineering capsids to optimize these interactions is a central strategy in developing next-generation gene therapies to enhance efficacy and minimize off-target effects (Li & Samulski, 2020, Nat. Rev. Genet.).

Other names

Adeno-associated virus receptorsAAV entry factorsAAV attachment factorsAAVRKIAA0319LHSPG-binding factors

Viral capsid binding to specific cell surface glycans and protein receptors triggers receptor-mediated endocytosis, facilitating the delivery of therapeutic genetic material into the host cell nucleus.