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Recent Advances in Vision Science
National Eye Institute Science Advances

Gene Therapy with a Promoter Targeting both Rods and Cones Rescues Retinal Degeneration caused by AIPL1 Mutations


Mutations in the gene that encodes the protein aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) are know to cause Leber congenital amaurosis (LCA), a severe, early-onset retinal degenerative disease. The gene is known to be expressed in both rod and cone photoreceptors in the retina. Retinal degenerative diseases are particularly well-suited to gene transfer but thus far, targeted diseases result from genes that are expressed in just one cell type. To treat AIPL1 induced LCA, requires development of a vector that can target two different cell types.


A recent laboratory study evaluated a new vector driven by a promoter that has affinity for both rod and cone cells. Use of this vector with the human rodopsin kinase (RK) promoter resulted in substantial rescue of the disease phenotype in mice harboring mutations in the AIPL1 loci. After administration of the vector, increased production of human AIPL1 in photoreceptor cells was found. As a result, retinal degeneration was significantly slowed and improved photoreceptor cell survival, preservation of photoreceptor outer segments and stabilization of retinal function were observed. This is the first successful example of targeting a transgene construct to both rods and cones simultaneously with a single tissue-specific promoter.

Public Impact Statement/Significance:

These studies suggest that replacement gene therapy mediated by AAV vectors is a promising potential therapy for human retinal degenerations, especially for those severe forms such as LCA and RP that are unlikely to respond to more conservative forms of treatment.

Grant Support:

U.S. National Institutes of Health, National Eye Institute (EY10581; P30EY14104).

Publication Citation and Link:

Sun, X. et al. Gene therapy with a promoter targeting both rods and cones rescues retinal degeneration caused by AIPL1 mutations. Gene Therapy. 2010; 17: 117-131. PubMed

Last Reviewed: January 2010

Department of Health and Human Services NIH, the National Institutes of Health