Year: 2020
Type: article
Abstract: Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.
Source: Protein & Cell
Authors: Fang Wang, Weiqi Zhang, Qiaoyan Yang, Yu Kang, Yanling Fan, Jingkuan Wei, Zunpeng Liu, Shaoxing Dai, Hao Li, Zifan Li, Lizhu Xu, Chu Chu, Jing Qu, Chenyang Si, Weizhi Ji, Guang-Hui Liu, Chengzu Long, Yuyu Niu
Institutions: Kunming University of Science and Technology, Chinese Academy of Sciences, Beijing Institute of Genomics, University of Chinese Academy of Sciences, NYU Langone Health, New York University, Institute of Zoology, State Key Laboratory of Stem Cell and Reproductive Biology, Capital Medical University, Xuan Wu Hospital of the Capital Medical University, State Key Laboratory of Membrane Biology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid:
OpenAlex ID: W3045582016