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Mol Ther. 2018 Nov 7;26(11):2631-2637. doi: 10.1016/j.ymthe.2018.08.007. Epub 2018 Aug 14.

Correction of the Marfan Syndrome Pathogenic FBN1 Mutation by Base Editing in Human Cells and Heterozygous Embryos.

Author information

1
Department of Reproductive Medicine, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, P.R. China.
2
School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Pudong New Area, Shanghai 201210, China.
3
Department of Reproductive Medicine, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, P.R. China; Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, P.R. China.
4
Department of Reproductive Medicine, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, P.R. China. Electronic address: liujqssz@gzhmu.edu.cn.
5
School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Pudong New Area, Shanghai 201210, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Electronic address: huangxx@shanghaitech.edu.cn.

Abstract

There are urgent demands for efficient treatment of heritable genetic diseases. The base editing technology has displayed its efficiency and precision in base substitution in human embryos, providing a potential early-stage treatment for genetic diseases. Taking advantage of this technology, we corrected a Marfan syndrome pathogenic mutation, FBN1T7498C. We first tested the feasibility in mutant cells, then successfully achieved genetic correction in heterozygous human embryos. The results showed that the BE3 mediated perfect correction at the efficiency of about 89%. Importantly, no off-target and indels were detected in any tested sites in samples by high-throughput deep sequencing combined with whole-genome sequencing analysis. Our study therefore suggests the efficiency and genetic safety of correcting a Marfan syndrome (MFS) pathogenic mutation in embryos by base editing.

KEYWORDS:

base editing; human embryos; pathogenic mutation

PMID:
30166242
PMCID:
PMC6224777
[Available on 2019-11-07]
DOI:
10.1016/j.ymthe.2018.08.007
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