Highly efficient transduction and lateral spread in the retina by a novel AAV virus enhanced by rational design

摘要

The present disclosure provides rAAV particles containing the novel capsid variant AAV44.9 (E531D). The present disclosure also provides rAAV particles containing AAV44.9 (E531D) for the treatment of the eye, including the treatment of retinal disorders. In a specific embodiment, the present disclosure exhibits an enhanced lateral spread after subretinal injection into the fovea of the subject, where foveal detachment is minimized. , AAV44.9 (E531D) provide rAAV particles containing capsid. The present disclosure further provides rAAV particles comprising an AAV44.9 (E531D) capsid, and a polynucleotide encoding a heterologous nucleic acid sequence. Also provided are methods of treatment involving administration of rAAV particles to mammals in need thereof, and methods of transducing photoreceptor cells and RPE cells with rAAV particles.