Integrin subunit alpha V (ITGAV)

Integrin subunit alpha V (ITGAV), also known as CD51, is a transmembrane glycoprotein that forms heterodimeric receptors with various beta subunits to facilitate cell-matrix and cell-cell interactions (UniProt P06756). It is a critical component of the vitronectin receptor and plays significant roles in signal transduction, angiogenesis, and tissue repair (NCBI Gene ID: 3685). In the field of gene therapy, ITGAV has been identified as the primary muscle-cell-surface receptor mediating the transduction of AAVMYO3, an engineered adeno-associated virus (AAV) capsid designed for high-efficiency delivery to skeletal and cardiac muscle (Tabebordbar et al., 2021, Cell). AAVMYO3 was developed through directed evolution and contains a specific peptide motif that binds with high affinity to ITGAV-containing heterodimers on the sarcolemma of muscle cells. This interaction enables the capsid to bypass liver sequestration and achieve potent, muscle-specific gene expression, which is a major hurdle for treating neuromuscular diseases like Duchenne muscular dystrophy. Beyond its role as a viral entry point, ITGAV is involved in the progression of various cancers and fibrotic diseases, making it a target for both delivery and direct therapeutic inhibition (PubMed: 18593951). The use of ITGAV as a docking site for AAVMYO3 represents a breakthrough in the development of targeted genetic medicines.

Other names

ITGAVCD51Integrin alpha-VMSK24VNRAVitronectin receptor subunit alphaAntigen CD51

AAVMYO3 acts as a ligand that binds to Integrin alpha-V heterodimers on the muscle cell surface, triggering receptor-mediated endocytosis and subsequent viral transduction of genetic material.