Ovando-Roche Patrick, Georgiadis Anastasios, Smith Alexander J, Pearson Rachael A, Ali Robin R
Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL UK.
Curr Stem Cell Rep. 2017;3(2):112-123. doi: 10.1007/s40778-017-0078-4. Epub 2017 Apr 18.
A major cause of visual disorders is dysfunction and/or loss of the light-sensitive cells of the retina, the photoreceptors. To develop better treatments for patients, we need to understand how inherited retinal disease mutations result in the dysfunction of photoreceptors. New advances in the field of stem cell and gene editing research offer novel ways to model retinal dystrophies in vitro and present opportunities to translate basic biological insights into therapies. This brief review will discuss some of the issues that should be taken into account when carrying out disease modelling and gene editing of retinal cells. We will discuss (i) the use of human induced pluripotent stem cells (iPSCs) for disease modelling and cell therapy; (ii) the importance of using isogenic iPSC lines as controls; (iii) CRISPR/Cas9 gene editing of iPSCs; and (iv) in vivo gene editing using AAV vectors.
Ground-breaking advances in differentiation of iPSCs into retinal organoids and methods to derive mature light sensitive photoreceptors from iPSCs. Furthermore, single AAV systems for in vivo gene editing have been developed which makes retinal in vivo gene editing therapy a real prospect.
Genome editing is becoming a valuable tool for disease modelling and in vivo gene editing in the retina.
视觉障碍的一个主要原因是视网膜的感光细胞（光感受器）功能障碍和/或丧失。为了给患者开发更好的治疗方法，我们需要了解遗传性视网膜疾病突变如何导致光感受器功能障碍。干细胞和基因编辑研究领域的新进展提供了在体外模拟视网膜营养不良的新方法，并为将基本生物学见解转化为治疗方法提供了机会。本简要综述将讨论在进行视网膜细胞疾病建模和基因编辑时应考虑的一些问题。我们将讨论：（i）使用人类诱导多能干细胞（iPSC）进行疾病建模和细胞治疗；（ii）使用同基因iPSC系作为对照的重要性；（iii）iPSC的CRISPR/Cas9基因编辑；以及（iv）使用腺相关病毒（AAV）载体进行体内基因编辑。
在将iPSC分化为视网膜类器官以及从iPSC衍生成熟感光光感受器的方法方面取得了突破性进展。此外，已经开发出用于体内基因编辑的单AAV系统，这使得视网膜体内基因编辑治疗成为一个切实可行的前景。
基因组编辑正成为视网膜疾病建模和体内基因编辑的一种有价值的工具。
