Pharmaceutical Development of AAV-Based Gene Therapy Products for the Eye

Abstract A resurgence of interest and investment in the field of gene therapy, driven in large part by advances in viral vector technology, has recently culminated in United States Food and Drug Administration approval of the first gene therapy product targeting a disease caused by mutations in a single gene. This product, LUXTURNA™ (voretigene neparvovec-rzyl; Spark Therapeutics, Inc., Philadelphia, PA), delivers a normal copy of the RPE65 gene to retinal cells for the treatment of biallelic RPE65 mutation–associated retinal dystrophy, a blinding disease. Many additional gene therapy programs targeting both inherited retinal diseases and other ocular diseases are in development, owing to an improved understanding of the genetic basis of ocular disease and the unique properties of the ocular compartment that make it amenable to local gene therapy. Here we review the growing body of literature that describes both the design and development of ocular gene therapy products, with a particular emphasis on target and vector selection, and chemistry, manufacturing, and controls.