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Review
. 2015 Jan 29;5(9):a017285.
doi: 10.1101/cshperspect.a017285.

The Status of RPE65 Gene Therapy Trials: Safety and Efficacy

Eric A Pierce  1 , Jean Bennett  2
Affiliations
Review

The Status of RPE65 Gene Therapy Trials: Safety and Efficacy

Eric A Pierce et al. Cold Spring Harb Perspect Med. .

Abstract

Several groups have reported the results of clinical trials of gene augmentation therapy for Leber congenital amaurosis (LCA) because of mutations in the RPE65 gene. These studies have used subretinal injection of adeno-associated virus (AAV) vectors to deliver the human RPE65 cDNA to the retinal pigment epithelial (RPE) cells of the treated eyes. In all of the studies reported to date, this approach has been shown to be both safe and effective. The successful clinical trials of gene augmentation therapy for retinal degeneration caused by mutations in the RPE65 gene sets the stage for broad application of gene therapy to treat retinal degenerative disorders.

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Figures

Figure 1.
Figure 1.
Frames from an intraoperative video of surgical delivery of AAV2-hRPE65.v2 in a Phase I/II clinical trial at CHOP. (A) A drop of dense Perfluoron liquid is layered onto the fovea to buttress it during the retinal detachment. (B) The subretinal injection cannula is opposed to the neural retina. Injection of the excipient (containing the AAV) causes a separation between the neural retina and the underlying retinal pigment epithelium (i.e., a localized retinal detachment). (C) A view of the detached region of the retina at lower magnification. The optic disk is visible and the detachment includes the superior arcade and extends through the fovea. A few small bubbles, introduced with the AAV, are now visible in the subretinal space.
See this image and copyright information in PMC

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