Optimization of AAV-mediated photoreceptor gene transfer for gene therapy of bPDE and AIPL1 deficiencies

Leader of the WP is Alberto Auricchio from the Telethon Institute of Genetics and Medicine (Naples, Italy).

The goal of WP1 is to obtain physiological levels of bPDE and AIPL1 expression by AAV-mediated somatic gene transfer using combinations of promoters and AAV serotypes.

Retinal gene transfer using vectors derived from the small adeno-associated virus (AAV) holds promise for the treatment of inherited retinal diseases. Dozens of different AAV serotypes have been isolated, which have different tropism and transduction characteristics. We have recently shown by quantitative analyses that AAV2/8 and the 800 bp proximal region of the human rhodopsin promoter provides the highest levels of murine photoreceptor transduction among the serotypes and promoters tested. In a gene therapy setting, the expression of the transgene should be kept at physiological levels to reach optimal therapeutic effect but avoiding potential toxicity due to overexpression. In order to achieve this we will evaluate a number of specific endogenous promoter fragments within various AAV serotypes.