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Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors

Published on Dec 1, 2019in Genome Biology 13.21
· DOI :10.1186/s13059-019-1703-6
Abstract
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References14
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Published on Feb 28, 2019in Science 41.06
Erwei Zuo3
Estimated H-index: 3
(CAS: Chinese Academy of Sciences),
Yidi Sun7
Estimated H-index: 7
(CAS-MPG Partner Institute for Computational Biology)
+ 7 AuthorsHui Yang16
Estimated H-index: 16
(CAS: Chinese Academy of Sciences)
Genome editing holds promise for correcting pathogenic mutations. However, it is difficult to determine off-target effects of editing due to single nucleotide polymorphism in individuals. Here, we developed a method named GOTI (Genome-wide Off-target analysis by Two-cell embryo Injection) to detect off-target mutations by editing one blastomere of two-cell mouse embryos using either CRISPR-Cas9 or base editors. Comparison of the whole genome sequences of progeny cells of edited vs. non-edited bl...
21 Citations Source Cite
Published on Feb 28, 2019in Science 41.06
Shuai Jin3
Estimated H-index: 3
(CAS: Chinese Academy of Sciences),
Yuan Zong6
Estimated H-index: 6
(CAS: Chinese Academy of Sciences)
+ 8 AuthorsFeng Zhang104
Estimated H-index: 104
(UMN: University of Minnesota)
Cytosine and adenine base editors (CBEs and ABEs) are promising new tools for achieving the precise genetic changes required for disease treatment and trait improvement. However, genome-wide and unbiased analyses of their off-target effects in vivo are still lacking. Our whole genome sequencing (WGS) analysis of rice plants treated with BE3, high-fidelity BE3 (HF1-BE3), or ABE revealed that BE3 and HF1-BE3, but not ABE, induce substantial genome-wide off-target mutations, which are mostly the C→...
16 Citations Source Cite
Published on Nov 1, 2018in Molecular Therapy 7.01
Yanting Zeng2
Estimated H-index: 2
(Guangzhou Medical University),
Jianan Li8
Estimated H-index: 8
(ShanghaiTech University)
+ 7 AuthorsXingxu Huang14
Estimated H-index: 14
(CAS: Chinese Academy of Sciences)
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, FBN1 T7498C . We first tested the feasibility in mutant cells, then successfully achieved genetic correction in heterozygous human embryos. The results sho...
13 Citations Source Cite
Published on Nov 1, 2017in Protein & Cell 6.23
Puping Liang7
Estimated H-index: 7
(SYSU: Sun Yat-sen University),
Chenhui Ding14
Estimated H-index: 14
(SYSU: Sun Yat-sen University)
+ 13 AuthorsYongxiang Liu1
Estimated H-index: 1
(SYSU: Sun Yat-sen University)
β-Thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB −28 (A>G) mutations is one of the three most common mutations in China and Southeast Asia patients with β-thalassemia. Correcting this mutation in human embryos may prevent the disease being passed onto future generations and cure anemia. Here we report the first study using base editor (BE) system to correct disease mutant in human embryos. Firstly, we produced a 293T cell line with an exogen...
38 Citations Source Cite
Published on Nov 1, 2017in Nature 41.58
Nicole M. Gaudelli5
Estimated H-index: 5
,
Alexis C. Komor12
Estimated H-index: 12
+ 4 AuthorsDavid R. Liu69
Estimated H-index: 69
A new DNA ‘base editor’ can change targeted A•T base pairs to G•C, allowing disease-associated mutations to be corrected and disease-suppressing mutations to be introduced into cells.
309 Citations Source Cite
Published on Oct 1, 2017in Protein & Cell 6.23
Guanglei Li4
Estimated H-index: 4
(Guangzhou Medical University),
Yajing Liu6
Estimated H-index: 6
(ShanghaiTech University)
+ 8 AuthorsXingxu Huang14
Estimated H-index: 14
(ShanghaiTech University)
21 Citations Source Cite
Published on Oct 1, 2017in Protein & Cell 6.23
Changyang Zhou3
Estimated H-index: 3
(CAS: Chinese Academy of Sciences),
Meiling Zhang2
Estimated H-index: 2
(SJTU: Shanghai Jiao Tong University)
+ 9 AuthorsWeiping Li7
Estimated H-index: 7
(SJTU: Shanghai Jiao Tong University)
16 Citations Source Cite
Published on Aug 1, 2017in Nature 41.58
Hong Ma27
Estimated H-index: 27
(Oregon National Primate Research Center),
Nuria Marti-Gutierrez1
Estimated H-index: 1
(OHSU: Oregon Health & Science University)
+ 28 AuthorsRiffat Ahmed10
Estimated H-index: 10
(OHSU: Oregon Health & Science University)
CRISPR–Cas9 genome editing is used to induce a DNA repair response and correct a disease-causing heterozygous mutation in human embryos with reduced mosaicism and preferential repair using the wild-type copy of the gene.
259 Citations Source Cite
Published on Jul 1, 2017in Cell Research 15.39
Erwei Zuo3
Estimated H-index: 3
,
Yijun Cai7
Estimated H-index: 7
+ 26 AuthorsWei Wei44
Estimated H-index: 44
One-step generation of complete gene knockout mice and monkeys by CRISPR/Cas9-mediated gene editing with multiple sgRNAs
35 Citations Source Cite
Published on May 1, 2017in Nature Biotechnology 35.72
Kyoungmi Kim4
Estimated H-index: 4
,
Seuk-Min Ryu5
Estimated H-index: 5
+ 6 AuthorsJin-Soo Kim52
Estimated H-index: 52
Mice with targeted point mutations are generated efficiently using Cas9–cytidine deaminase fusions.
112 Citations Source Cite
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