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Efficient generation of pathogenic A-to-G mutations in human tripronuclear embryos via ABE-mediated base editing

Published on Jun 1, 2019in Molecular therapy. Nucleic acids 5.66
· DOI :10.1016/j.omtn.2019.05.021
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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 Sep 1, 2018in Nature 41.58
Pinar Akcakaya2
Estimated H-index: 2
(AstraZeneca),
Maggie L. Bobbin4
Estimated H-index: 4
(Harvard University)
+ 19 AuthorsAlba Carreras2
Estimated H-index: 2
(AstraZeneca)
CRISPR–Cas genome-editing nucleases hold substantial promise for developing human therapeutic applications1–6 but identifying unwanted off-target mutations is important for clinical translation7. A well-validated method that can reliably identify off-targets in vivo has not been described to date, which means it is currently unclear whether and how frequently these mutations occur. Here we describe ‘verification of in vivo off-targets’ (VIVO), a highly sensitive strategy that can robustly identi...
28 Citations Source Cite
Published on Mar 1, 2018in Clinical Chemistry 8.64
Nicholas Katsanis77
Estimated H-index: 77
(Duke University)
The observation that the human genome can be mapped represented a major inflection point in biology. The decision to sequence the human genome was met with excitement and trepidation. The arguments for and against sequencing included whether the technology was sufficiently advanced, whether it would divert resources from elsewhere, and whether it could have unknown negative societal benefits. Some 2 decades later, the delivery of the first draft of the human genome was received as a crowning ach...
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Published on Feb 7, 2018in Frontiers in Genetics 4.15
Ianis G. Matsoukas4
Estimated H-index: 4
(University of Bolton)
2 Citations Source Cite
Published on Nov 1, 2017in Protein & Cell 6.23
Xiang Jin Kang1
Estimated H-index: 1
(Guangzhou Medical University),
Chiong Isabella Noelle Caparas1
Estimated H-index: 1
(Agency for Science, Technology and Research)
+ 1 AuthorsYong Fan12
Estimated H-index: 12
(Guangzhou Medical University)
7 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
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