Lentiviral vectors containing a retinal pigment epithelium specific promoter for leber congenital amaurosis gene therapy. Lentiviral gene therapy for LCA.

摘要

Oculogenetics Unit, Hopital Ophtalmique Jules Gonin, Lausanne, Switzerland Leber congenital amaurosis (ICA) is a retinitis pigmontosa with early onset, leading to blindness in infants. There is currently no efficient therapy to treat LCA. At the present time, mutations in seven different genes have been associated with the disease (Hanein et al. 2004). In 10 to 15% of the cases LCA originates from a mutation in RPE65 (Gu et al. 1997), a gene specifically expressed in the cells of the retinal pigment epithelium layer (RPE cells). This gene encodes a 65 kD protein the function of which has been dissected in a recently published study demonstrating its crucial role as a regulator of the visual cycle and a chaperone for the chromophore of the visual pigment (Xue et al. 2004). The patients affected by a mutation in this gene could benefit from a substitutive gene therapy consisting in the transfer of a fully functional allele of the RPE65 gene in RPE cells. Furthermore, animal models of RPE6(5 mutations have been identified (Aguirre et al. 1998; Veske et al. 1999) or genetically produced (Redmond et al. 1998) and thus provide the necessary tools to set up the conditions of such a strategy before a clinical trial can be started. The proof