Retinal cell surface receptors for engineered AAV capsids

Retinal cell surface receptors and attachment factors for engineered Adeno-Associated Virus (AAV) capsids are the molecular entities that mediate the binding and entry of synthetic viral vectors into retinal cells. While the Adeno-associated virus receptor (AAVR or KIAA0319L) has been identified as a universal entry factor for most natural AAV serotypes (Pillay et al., 2016, Nature), engineered capsids often utilize distinct, unidentified receptors to improve retinal penetration. For instance, the engineered AAV2-7m8 variant was designed to bypass the inner limiting membrane, yet its specific high-affinity binding partners in the outer retina remain largely uncharacterized (Dalkara et al., 2013, Science Translational Medicine). These unidentified factors are critical for the success of gene therapies targeting inherited retinal degenerations, such as Leber congenital amaurosis or retinitis pigmentosa. In these applications, the AAV capsid acts as the delivery vehicle that targets these surface molecules to internalize genetic payloads. Identifying these specific molecules is a significant challenge in the field, as it would allow for more precise engineering of vectors for treating inherited retinal diseases. Currently, the interaction between engineered capsids and these unknown surface factors is the primary mechanism for delivering corrective genes in clinical and preclinical ocular therapies (Huang et al., 2023, Nature Communications).

Other names

Unidentified retinal AAV receptorsAAV attachment factorsEngineered AAV binding partnersRetinal AAV entry factorsAAV capsid receptors

Facilitation of viral attachment and internalization into retinal cells for gene delivery