First Gene Therapy FDA-Approved for an Inherited Retinal Disease

The approval has stimulated research into gene therapies for other IRDs.

Meghan J. DeBenedictis, MS, LGC, MEd, and Aleksandra V. Rachitskaya, MD





The idea of gene therapy has been discussed in the medical literature since as early as the 1970s. In 1972, Friedman and Roblin proposed that it was theoretically possible to introduce “good” DNA to replace defective DNA. Over the years, a number of gene therapy clinical trials emerged in efforts to treat genetic diseases of inborn errors of metabolism, all with varying degrees of success.


The basic principle of gene therapy is to put corrective genetic material into cells to treat genetic disease. Several gene therapy approaches, including replacement gene therapy, optogenetics, addition of a growth factor, suppression gene therapy, and gene editing, have been proposed in attempts to treat various ophthalmologic conditions.

Optogenetics focuses on creating artificial photoreceptors to restore photosensitivity. This is accomplished by gene delivery of light-activated optogenetic tools (channels or pumps) to surviving cells, such as ganglion cells, that remain intact in the retinal circuit in various diseases. It has been posited that genetically added growth factor proteins, such as adenovirus-expressed endostatin and angiostatin gene products, could have anti-VEGF properties. Short-interfering RNAs could be used for down-regulation of gene expression, resulting in functional inactivation of the targeted genes.4 Finally, technologies such as CRISPR (standing for clustered regularly interspaced short palindromic repeats) could allow editing of one or several sites within the mammalian genome.

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Meghan J. DeBenedictis, MS, LGC, MEd

  • Licensed, Certified Genetic Counselor, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio

  • marinom2@ccf.org

  • Financial Disclosure: Consultant (Spark Therapeutics, Second Sight Medical Products)

Aleksandra V. Rachitskaya, MD

  • Vitreoretinal Physician, Cole Eye Institute, Cleveland Clinic Foundation, and Assistant Professor of Ophthalmology, Cleveland Clinic Lerner College of Medicine; both in Cleveland, Ohio

  • rachita@ccf.org

  • Financial Disclosure: None