Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, WI, USA.
Adv Exp Med Biol. 2019;1185:79-83. doi: 10.1007/978-3-030-27378-1_13.
The ability to temporally control levels of a therapeutic protein in vivo is vital for the development of safe and efficacious gene therapy treatments for autosomal dominant or complex retinal diseases, where uncontrolled transgene overexpression may lead to deleterious off-target effects and accelerated disease progression. While numerous platforms exist that allow for modulation of gene expression levels - ranging from inducible promoters to destabilizing domains - many have drawbacks that make them less than ideal for use in recombinant adeno-associated virus (rAAV) vectors, which over the past two decades have become the mainstay technology for mediating gene delivery to the retina. Herein, we discuss the advantages and disadvantages of three major gene expression platforms with regard to their suitability for ocular gene therapy applications.
在体内对治疗性蛋白质的水平进行时间控制的能力对于开发安全有效的常染色体显性或复杂视网膜疾病的基因治疗至关重要，因为不受控制的转基因过表达可能导致有害的脱靶效应和加速疾病进展。虽然有许多平台可以调节基因表达水平，范围从诱导启动子到不稳定域，但许多平台都存在缺陷，使其不太适合用于重组腺相关病毒 (rAAV) 载体，rAAV 载体在过去二十年中已成为介导基因递送至视网膜的主要技术。在此，我们将讨论三种主要基因表达平台在用于眼部基因治疗应用方面的优缺点。
