Emilia A. Zin1, Bilge E. Ozturk2, Deniz Dalkara1 and Leah C. Byrne2,3,4 1Sorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, France 2Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA 3Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA 4Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA Correspondence: deniz.dalkaragmail.com; lbyrnepitt.edu

Since their discovery over 55 years ago, adeno-associated virus (AAV) vectors have become powerful tools for experimental and therapeutic in vivo gene delivery, particularly in the retina. Increasing knowledge of AAV structure and biology has propelled forward the development of engineered AAV vectors with improved abilities for gene delivery. However, major obstacles to safe and efficient therapeutic gene delivery remain, including tropism, inefficient and untargeted gene delivery, and limited carrying capacity. Additional improvements to AAV vectors will be required to achieve therapeutic benefit while avoiding safety issues. In this review, we provide an overview of recent methods for engineering-enhanced AAV capsids, as well as remaining challenges that must be overcome to achieve optimized therapeutic gene delivery in the eye.