AAV-PHP.eB transduces both the inner and outer retina with high efficacy in mice
Arpad Palfi, Naomi Chadderton, Sophia Millington‐Ward, Iris J. M. Post, Pete Humphries, Paul F. Kenna, G. Jane Farrar
Abstract
directed evolution, which can cross the blood-brain barrier and target neurons with high efficacy in mice. Systemic and intravitreal delivery of AAV-PHP.eB resulted in the high transduction efficacy of retinal ganglion and horizontal cells, with systemic delivery providing pan-retinal coverage of the mouse retina. Subretinal delivery transduced photoreceptors and retinal pigment epithelium cells robustly. EGFP expression (number of transduced cells and mRNA levels) were similar when the retinas were transduced systemically or intravitreally with AAV-PHP.eB or intravitreally with AAV2/2. Notably, in photoreceptors, EGFP fluorescence intensities and mRNA levels were 50-70 times higher, when subretinal injections with AAV-PHP.eB were compared to AAV2/8. Our results demonstrate the pan-retinal transduction of ganglion cells and extremely efficient transduction of photoreceptor and retinal pigment epithelium cells as the most valuable features of AAV-PHP.eB in the mouse retina.