Application of CRISPR/Cas9 technologies combined with iPSCs in the study and treatment of retinal degenerative diseases

Abstract

Retinal degeneration diseases, such as age-related macular degeneration and retinitis pigmentosa, affect millions of people worldwide and are major causes of irreversible blindness. Effective treatments for retinal degeneration, including drug therapy, gene augmentation or transplantation approaches, have been widely investigated. Nevertheless, more research should be dedicated to therapeutic methods to improve future clinical treatments. Recently, with the rapid development of genome-editing technology, gene therapy has become a potentially effective treatment for retinal degeneration diseases. A clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has been developed as a powerful genome-editing tool in ophthalmic studies. The CRISPR/Cas9 system has been widely applied in basic research to develop animal models and gene therapies in vivo. With the ability to self-renew and the potential to differentiate into different types of cells, induced pluripotent stem cells (iPSCs) have already been used as a promising tool for understanding disease pathophysiology and evaluating the effect of drug and gene therapeutics. iPSCs are also a cell source for autologous transplantation. In this review, we compared genome-editing strategies and highlighted the advantages and concerns of the CRISPR/Cas9 system. Moreover, the latest progress and applications of the CRISPR/Cas9 system and its combination with iPSCs for the treatment of retinal degenerative diseases are summarized.

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(reprinted from Liao et al. (2017), Copyright (2017), with permission from Elsevier)

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Acknowledgements

We thank Jin Yang, Xiaomin Zhang and Xiaorong Li for comments and suggestions, Jin Yang and Zhiqing Li for editing the manuscript, Bincui Cai for writing the manuscript, and Shuo Sun for assistance in generating the table. This work was supported by the National Natural Science Foundation (81670875; 81500745), China; the Natural Science Foundation of Tianjin City (18JCQNJC10700); the Natural Science Foundation of Tianjin City (17JCYBJC27200); and a grant from the Dr. Henry Norman Bethune: LangMu Young Scientist Scholarship (BJ-LM2015008L).

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Correspondence to Jin Yang or Xiaorong Li.

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Cai, B., Sun, S., Li, Z. et al. Application of CRISPR/Cas9 technologies combined with iPSCs in the study and treatment of retinal degenerative diseases. Hum Genet 137, 679–688 (2018). https://doi.org/10.1007/s00439-018-1933-9

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