Transduction of retinal pigment epithelial cells with an adeno-associated viral vector (AAV) based on serotype 2 has partially corrected retinal blindness in Leber congenital amaurosis type 2. However, many applications of gene therapy for retinal blindness rely on the efficient transduction of rod and cone photoreceptor which is difficult to achieve with first generation vector technology. To address this translational need, we evaluated rod and cone photoreceptor targeting of 4 novel AAV capsids (AAV7, AAV9, rh.64R1 and rh.8R) versus AAV2 and AAV8 in a foveated retina. Eyes of 20 nonhuman primates were injected subretinally in the proximity of the fovea. While numerous vectors efficiently transduced rods, only AAV9 targeted cones both centrally and peripherally efficiently at low doses, likely due to the abundance of galactosylated glycans, the primary receptor for AAV9, on cone photoreceptors. We conclude AAV9 is an ideal candidate for strategies that require restoration of cone photoreceptor function.

In a large inner-city teaching hospital, only 28 percent of over 1000 consecutive hospital admissions received proper screening for diseases of substance abuse. Although the CAGE questions are currently considered the best screening test for quickly assessing an alcohol abuse history, not a single CAGE question was documented during our 23 day study. Of the 1010 patients in the study, 160 or 16% were found to be substance abusers. Of these, 57 (37%) were properly screened by the physician team and 8 (5%) received adequate follow-up treatment for their substance abuse by way of social service or psychiatric consultation, or documented counselling by their physician. Physicians are not adequately screening for the diseases of substance abuse, and are not appropriately evaluating and referring patients who are known to be substance abusers. Meaningful training of medical students and physicians is necessary to increase awareness and produce positive behavior change.

Transduction of retinal pigment epithelial cells with an adeno-associated viral vector (AAV) based on serotype 2 has partially corrected retinal blindness in Leber congenital amaurosis type 2. However, many applications of gene therapy for retinal blindness rely on the efficient transduction of rod and cone photoreceptor which is difficult to achieve with first generation vector technology. To address this translational need, we evaluated rod and cone photoreceptor targeting of 4 novel AAV capsids (AAV7, AAV9, rh.64R1 and rh.8R) versus AAV2 and AAV8 in a foveated retina. Eyes of 20 nonhuman primates were injected subretinally in the proximity of the fovea. While numerous vectors efficiently transduced rods, only AAV9 targeted cones both centrally and peripherally efficiently at low doses, likely due to the abundance of galactosylated glycans, the primary receptor for AAV9, on cone photoreceptors. We conclude AAV9 is an ideal candidate for strategies that require restoration of cone photoreceptor function.

No abstract