Zin Emilia A, Ozturk Bilge E, Dalkara Deniz, Byrne Leah C
Sorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, France.
Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Cold Spring Harb Perspect Med. 2023 Mar 27;13(12). doi: 10.1101/cshperspect.a041291.
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.
自55多年前被发现以来，腺相关病毒（AAV）载体已成为体内实验性和治疗性基因递送的强大工具，尤其是在视网膜中。对AAV结构和生物学的了解不断增加，推动了具有改进基因递送能力的工程化AAV载体的开发。然而，安全有效的治疗性基因递送仍存在主要障碍，包括嗜性、低效和非靶向基因递送以及携带能力有限。为了在避免安全问题的同时实现治疗益处，需要对AAV载体进行进一步改进。在这篇综述中，我们概述了工程增强型AAV衣壳的最新方法，以及在眼睛中实现优化治疗性基因递送必须克服的剩余挑战。
