HIGHLY EFFICIENT TRANSDUCTION AND LATERAL SPREAD IN THE RETINA BY A NOVEL AAV VIRUS ENHANCED BY RATIONAL DESIGN

摘要

The disclosure provides rAAV particles comprising a new capsid variant, AAV44.9(E531D). The disclosure also provides rAAV particles comprising AAV44.9(E531D) for treatment of the eye, including treatment of retinal disorders. In particular embodiments, the disclosure provides rAAV particles comprising an AAV44.9(E531D) capsid that exhibits enhanced lateral spread after subretinal injection to a fovea of the subject, wherein detachment of the fovea is minimized. The disclosure further provides rAAV particles comprising an AAV44.9(E531D) capsid and a polynucleotide encoding a heterologous nucleic acid sequence. Methods of treatment comprising administering rAAV particles to a mammal in need thereof, and methods of transducing photoreceptor and RPE cells with rAAV particles, are also provided.