MiniCAFE, a CRISPR/Cas9-based compact and potent transcriptional activator, elicits gene expression in vivo

Author:

Zhang Xin1,Lv Sihan2,Luo Zhenhuan34,Hu Yongfei56,Peng Xin1,Lv Jie1,Zhao Shanshan1,Feng Jianqi1,Huang Guanjie1,Wan Qin-Li34,Liu Jun6,Huang Hongxin6,Luan Bing2,Wang Dong56,Zhao Xiaoyang7,Lin Ying1,Zhou Qinghua34,Zhang Zhen-Ning8,Rong Zhili169ORCID

Affiliation:

1. Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China

2. Department of Endocrinology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China

3. Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China

4. The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou 510632, China

5. Department of Bioinformatics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China

6. Dermatology Hospital, Southern Medical University, Guangzhou 510091, China

7. Department of Development, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China

8. Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China

9. Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China

Abstract

Abstract CRISPR-mediated gene activation (CRISPRa) is a promising therapeutic gene editing strategy without inducing DNA double-strand breaks (DSBs). However, in vivo implementation of these CRISPRa systems remains a challenge. Here, we report a compact and robust miniCas9 activator (termed miniCAFE) for in vivo activation of endogenous target genes. The system relies on recruitment of an engineered minimal nuclease-null Cas9 from Campylobacter jejuni and potent transcriptional activators to a target locus by a single guide RNA. It enables robust gene activation in human cells even with a single DNA copy and is able to promote lifespan of Caenorhabditis elegans through activation of longevity-regulating genes. As proof-of-concept, delivered within an all-in-one adeno-associated virus (AAV), miniCAFE can activate Fgf21 expression in the liver and regulate energy metabolism in adult mice. Thus, miniCAFE holds great therapeutic potential against human diseases.

Funder

National Natural Science Foundation of China

National Key Research and Development Program of China

National Science and Technology Major Project

Frontier Research Program of Bioland Laboratory

Shanghai Scientific Research Project

Natural Science Foundation of Guangdong Province

Publisher

Oxford University Press (OUP)

Subject

Genetics

Cited by 32 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3