Heparan sulfate proteoglycan and N-linked sialic acid (HSPG/Sialic acid)

Skeletal muscle cell surface receptors for the AAV2.5 capsid primarily consist of heparan sulfate proteoglycans (HSPG) and N-linked sialic acid moieties [1, 4]. AAV2.5 is a synthetic, chimeric capsid engineered by grafting five amino acids from AAV1 onto an AAV2 scaffold to combine the heparin-binding affinity of AAV2 with the superior muscle tissue tropism of AAV1 [1, 5]. These receptors serve as the primary attachment factors, allowing the viral vector to dock onto the sarcolemma of skeletal muscle fibers before undergoing internalization via the universal adeno-associated virus receptor (AAVR/KIAA0319L) [2]. This receptor complex is a critical target for gene therapy applications, most notably in the treatment of Duchenne muscular dystrophy (DMD), where AAV2.5 has been used to deliver truncated dystrophin genes in clinical trials [3]. The efficiency of muscle transduction is directly dependent on the interaction between the engineered capsid and these surface glycans, making them central to the design of muscle-directed biologics. Understanding the density and distribution of these receptors is essential for optimizing vector dosing and managing potential immunogenic responses to the viral capsid [3, 5].

Other names

AAV2.5 receptorsSkeletal muscle AAV2.5 binding sitesHSPGN-linked sialic acidAdeno-associated virus receptor (AAVR)

Viral vector-mediated gene delivery via receptor-mediated endocytosis and intracellular trafficking to the nucleus.