RegenerativeMedicine.net

Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors

Authors: Jie Zhu, Chang Ming, Xin Fu, Yaou Duan, Duc Anh Hoang, Jeffrey Rutgard, Runze Zhang, Wenqiu Wang, Rui Hou, Daniel Zhang, Edward Zhang, Charlotte Zhang, Xiaoke Hao, Wenjun Xiong, Kang Zhang

Summary:

We report a gene therapy strategy using CRISPR/Cas9-mediated cellular reprogramming by switching a mutation-venerable/sensitive cell type to a mutation-insensitive/resistant cell type, therefore restoring tissue architecture and function. We applied this strategy to retinitis pigmentosa (RP), a major cause of blindness characterized by retinal rod photoreceptor degeneration caused by numerous mutations in many genes. By reprogramming rod to cone-like photoreceptors in situ by inactivating Nrl or Nr2e3, we show an increase in cone-like cells with remarkable concomitant preservation of both cone and rod photoreceptors and retinal tissue, with restoration of visual function. Our approach demonstrates the feasibility of cellular reprogramming in preventing degeneration and preserving tissue and function, and points to a novel approach in treating human diseases in a gene and mutation independent manner.

Source: Cell Research; 2017