Gene Therapy for Retinal Diseases Is Within Sight

Charles C. Wykoff, MD, PhD


May 07, 2014

In This Article

Why Target Retinal Disease With Gene Therapy?

Related to retinal disease management, "gene therapy" refers to the incorporation of new DNA into cells, either to supply a gene that is missing or not functioning in that cell or to supply a therapeutic gene. Several characteristics make the retina an ideal target for gene therapy:

The intraocular environment is easily accessed through the pars plana by a relatively noninvasive approach compared with other internal organs, and the amount of retinal tissue is relatively small compared with most visceral organ systems.

The blood-retinal barrier creates an intraocular environment that is relatively isolated from the systemic immune system, affording some degree of tolerance for administered foreign antigens and minimization of systemic vector spread.

Treatment outcomes can be easily monitored both subjectively (eg, with patient visual acuity) and objectively (eg, with electrophysiology and optical coherence tomography).

The ordered, epithelial architecture of retinal layers allows an administered vector easy access to entire cell populations.

The 3 most commonly used vector systems for retinal gene delivery are adenoviral vectors, lentiviral vectors, and recombinant adeno-associated virus (rAAV) vectors. The most widely used vectors for ocular gene therapy -- rAAV vectors -- do not contain viral genes but rather are engineered to contain specific DNA sequences that can be used for therapeutic purposes. rAAV is able to transduce both dividing and nondividing cells, and different serotypes can be used to preferentially target specific retinal cell types, including the photoreceptors, RPE, or ganglion cells.[12]

The combination of an accessible target tissue (the retina) with multiple monogenic blinding diseases with no available treatment spurred extensive research over the past 20 years. Building on successful animal models, we are currently witnessing the translation of this basic science research to human clinical application.


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