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[摘要]：Leber's congenital amaurosis (LCA) is a group of genetic disorders that produces defects in the retinal epithelium photoreceptors of the eye. It manifests at on early age, resulting in impaired vision and ultimately blindness. It is estimated that as many as 10% of children attending schools for the visually impaired suffer from this type of retinal disease. Lack of retinoid isomerohydrolase, a protein essential for correct photoreceptor function, due to a genetic mutation has been cited as a major cause of type 2 LCA (LCA2). Preclinical evidence from rodent and canine models has shown that gene therapy using a recombinant adeno-associated virus (rAAV) to deliver functional retinoid isomerohydrolase protein can successfully restore some degree of visual function in animal models of LA and can prevent associated retinal degeneration. Following this preclinical evidence, the University of Pennsylvania in collaboration with Applied Genetic Technologies has produced an rAAV vector that expresses the human protein under the control of a chicken beta-actin promoter. This construct is currently undergoing phase I and II clinical trials in patients with LCA2. Preliminary results indicate that subretinal injection of rAAV2-CBSB-hRPE65 does not produce any discernable adverse immunogenic response and can improve visual function over the long term in young adults diagnosed with LCA2. |
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