Developing New Vectors for Retinal Gene Therapy

Emilia A Zin; Bilge E Ozturk; Deniz Dalkara; Leah C Byrne

doi:10.1101/cshperspect.a041291

Developing New Vectors for Retinal Gene Therapy

Cold Spring Harb Perspect Med. 2023 Mar 27;13(12):a041291. doi: 10.1101/cshperspect.a041291. Online ahead of print.

Authors

Emilia A Zin¹, Bilge E Ozturk², Deniz Dalkara³, Leah C Byrne^{4

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Affiliations

¹ Sorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, France.
² Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
³ Sorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, France deniz.dalkara@gmail.com lbyrne@pitt.edu.
⁴ Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA deniz.dalkara@gmail.com lbyrne@pitt.edu.
⁵ Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
⁶ Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.

PMID: 36987583
PMCID: PMC10691475 (available on 2025-12-01)
DOI: 10.1101/cshperspect.a041291

Abstract

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.