Millette Katelyn, Georgia Senta
Center for Endocrinology, Diabetes and Metabolism, Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Departments of Pediatrics and Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Curr Diab Rep. 2017 Oct 5;17(11):116. doi: 10.1007/s11892-017-0947-3.
This review will focus on the multiple approaches to gene editing and address the potential use of genetically modified human pluripotent stem cell-derived beta cells (SC-β) as a tool to study human beta-cell development and model their function in diabetes. We will explore how new variations of CRISPR/Cas9 gene editing may accelerate our understanding of beta-cell developmental biology, elucidate novel mechanisms that establish and regulate beta-cell function, and assist in pioneering new therapeutic modalities for treating diabetes.
Improvements in CRISPR/Cas9 target specificity and homology-directed recombination continue to advance its use in engineering stem cells to model and potentially treat disease. We will review how CRISPR/Cas9 gene editing is informing our understanding of beta-cell development and expanding the therapeutic possibilities for treating diabetes and other diseases. Here we focus on the emerging use of gene editing technology, specifically CRISPR/Cas9, as a means of manipulating human gene expression to gain novel insights into the roles of key factors in beta-cell development and function. Taken together, the combined use of SC-β cells and CRISPR/Cas9 gene editing will shed new light on human beta-cell development and function and accelerate our progress towards developing new therapies for patients with diabetes.
本综述将聚焦于基因编辑的多种方法，并探讨基因修饰的人多能干细胞衍生的β细胞（SC-β）作为研究人类β细胞发育及模拟其在糖尿病中功能的工具的潜在用途。我们将探讨CRISPR/Cas9基因编辑的新变体如何加速我们对β细胞发育生物学的理解，阐明建立和调节β细胞功能的新机制，并助力开创治疗糖尿病的新疗法。
CRISPR/Cas9靶点特异性和同源定向重组的改进不断推动其在工程化干细胞以模拟和潜在治疗疾病方面的应用。我们将回顾CRISPR/Cas9基因编辑如何增进我们对β细胞发育的理解，并拓展治疗糖尿病及其他疾病的可能性。在此，我们重点关注基因编辑技术，特别是CRISPR/Cas9作为一种操纵人类基因表达以深入了解关键因子在β细胞发育和功能中作用的新兴用途。总之，SC-β细胞与CRISPR/Cas9基因编辑的联合应用将为人类β细胞发育和功能带来新的认识，并加速我们为糖尿病患者开发新疗法的进程。
