Integrin alpha-V beta-6, Integrin alpha-V beta-8, and Heparan Sulfate Proteoglycans (αvβ6/αvβ8/HSPG)

The AAV-MT capsid is an engineered adeno-associated virus (AAV) variant developed for targeted gene delivery to skeletal and cardiac muscle. It is a chimeric capsid derived from AAV9 and AAVrh74, featuring an RGD-containing peptide insertion that facilitates specific binding to cell-surface receptors (Puzzo et al., 2017; Ronzitti et al., 2017). Research has identified integrin alpha-V beta-6 (αvβ6) and integrin alpha-V beta-8 (αvβ8) as the primary protein receptors recognized by the AAV-MT capsid, which are highly expressed in muscle tissues (El Andari et al., 2022). Additionally, the capsid utilizes heparan sulfate proteoglycans (HSPG) as cell-surface attachment factors to enhance viral entry and transduction efficiency. By targeting these specific integrins and glycans, AAV-MT achieves superior muscle tropism and significant liver detargeting compared to natural serotypes like AAV9. This receptor-glycan complex is a critical target for next-generation gene therapies aimed at treating neuromuscular disorders such as Pompe disease and Duchenne muscular dystrophy, allowing for effective treatment at lower systemic doses and reducing the risk of liver-related adverse effects.

Other names

AAV-MT receptorMuscle-tropic AAV receptor complexIntegrin alpha-V beta-6Integrin alpha-V beta-8Heparan sulfate proteoglycansαvβ6αvβ8HSPG

Viral attachment and entry via RGD-integrin interaction and glycan-mediated attachment