CRISPR: Established Editor of Human Embryos?

Published on Sep 1, 2017in Cell Stem Cell 23.29
· DOI :10.1016/j.stem.2017.08.007
Xiao-Jiang Li61
Estimated H-index: 61
(Emory University),
Zhuchi Tu7
Estimated H-index: 7
(Jinan University)
+ 1 AuthorsLi Shihua76
Estimated H-index: 76
(Emory University)
Abstract
Off-target effects and mosaicism are major concerns for applying CRISPR-Cas9 to correct genetic mutations. A recent article in Nature by Ma et al. (2017) uses an elegant CRISPR-Cas9 approach that repairs a genetic mutation in human embryos with negligible mosaicism and no off-target effects, bringing this editing tool closer to clinical application.
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References10
Published on May 1, 2003in Reproduction 3.09
David W. McLay4
Estimated H-index: 4
,
Hugh J. Clarke25
Estimated H-index: 25
(McGill University)
At fertilization, the highly condensed and transcriptionally inert chromatin of the spermatozoa becomes remodelled into the decondensed and transcriptionally competent chromatin of the male pronucleus. The chromatin initially becomes dispersed and then transiently recondenses into a small mass upon entry into the ooplasm. This morphological change is coincident with and likely dependent on the replacement of the sperm-specific protamines by oocyte-supplied histones and the organization of the ch...
205 Citations Source Cite
Published on Apr 11, 2014in Science 41.06
Alexandre Orthwein9
Estimated H-index: 9
(Lunenfeld-Tanenbaum Research Institute),
Amélie Fradet-Turcotte18
Estimated H-index: 18
(Lunenfeld-Tanenbaum Research Institute)
+ 5 AuthorsDaniel Durocher52
Estimated H-index: 52
(University of Toronto)
Mitotic cells inactivate DNA double-strand break (DSB) repair, but the rationale behind this suppression remains unknown. Here, we unravel how mitosis blocks DSB repair and determine the consequences of repair reactivation. Mitotic kinases phosphorylate the E3 ubiquitin ligase RNF8 and the nonhomologous end joining factor 53BP1 to inhibit their recruitment to DSB-flanking chromatin. Restoration of RNF8 and 53BP1 accumulation at mitotic DSB sites activates DNA repair but is, paradoxically, delete...
147 Citations Source Cite
Published on Jul 1, 2015in Human Molecular Genetics 4.90
Yongchang Chen12
Estimated H-index: 12
(Kunming University of Science and Technology),
Yinghui Zheng3
Estimated H-index: 3
(Chinese Academy of Sciences)
+ 12 AuthorsRuxiao Xing3
Estimated H-index: 3
(Chinese Academy of Sciences)
CRISPR/Cas9 has been used to genetically modify genomes in a variety of species, including non-human primates. Unfortunately, this new technology does cause mosaic mutations, and we do not yet know whether such mutations can functionally disrupt the targeted gene or cause the pathology seen in human disease. Addressing these issues is necessary if we are to generate large animal models of human diseases using CRISPR/Cas9. Here we used CRISPR/Cas9 to target the monkey dystrophin gene to create mu...
88 Citations Source Cite
Published on May 1, 2009in Nature Medicine 32.62
Evelyne Vanneste13
Estimated H-index: 13
(Katholieke Universiteit Leuven),
Thierry Voet29
Estimated H-index: 29
(Katholieke Universiteit Leuven)
+ 12 AuthorsFrans Schuit58
Estimated H-index: 58
(Katholieke Universiteit Leuven)
Chromosome instability is a hallmark of tumorigenesis. This study establishes that chromosome instability is also common during early human embryogenesis. A new array-based method allowed screening of genome-wide copy number and loss of heterozygosity in single cells. This revealed not only mosaicism for whole-chromosome aneuploidies and uniparental disomies in most cleavage-stage embryos but also frequent segmental deletions, duplications and amplifications that were reciprocal in sister blasto...
461 Citations Source Cite
Published on May 1, 2015in Protein & Cell 6.23
Puping Liang6
Estimated H-index: 6
(Sun Yat-sen University),
Y. Xu5
Estimated H-index: 5
(Sun Yat-sen University)
+ 13 AuthorsYujing Li5
Estimated H-index: 5
(Sun Yat-sen University)
Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISP...
417 Citations Source Cite
Published on Dec 1, 2017in Scientific Reports 4.12
Zhuchi Tu7
Estimated H-index: 7
,
Weili Yang9
Estimated H-index: 9
+ 10 AuthorsSu Yang8
Estimated H-index: 8
18 Citations Source Cite
Published on Jun 1, 2017in Molecular Genetics and Genomics 2.73
Lichun Tang1
Estimated H-index: 1
(Protein Sciences),
Yanting Zeng1
Estimated H-index: 1
(Guangzhou Medical University)
+ 8 AuthorsXiaowei Li1
Estimated H-index: 1
(Nanjing University)
Previous works using human tripronuclear zygotes suggested that the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system could be a tool in correcting disease-causing mutations. However, whether this system was applicable in normal human (dual pronuclear, 2PN) zygotes was unclear. Here we demonstrate that CRISPR/Cas9 is also effective as a gene-editing tool in human 2PN zygotes. By injection of Cas9 protein complexed with the appropriate sgRNAs and homology donors into o...
74 Citations Source Cite
Published on Jun 1, 2017in Nature Methods 26.92
Kellie A. Schaefer4
Estimated H-index: 4
,
Wen-Hsuan Wu7
Estimated H-index: 7
+ 3 AuthorsVinit B. Mahajan24
Estimated H-index: 24
123 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
(Oregon Health & Science University)
+ 28 AuthorsRiffat Ahmed10
Estimated H-index: 10
(Oregon Health & Science University)
Genome editing could be applied to correct disease-causing mutations in human embryos, but concerns about efficacy and safety are paramount. Shoukhrat Mitalipov and colleagues use CRISPRCas9 to correct a heritable cardiomyopathy mutation in human embryos. By optimizing the experimental conditions, the authors show very reduced mosaicism, and report that for this heterozygous mutation, CRISPRCas9-induced breaks seem to be preferentially repaired using the wild-type allele as a template in human e...
238 Citations Source Cite
Published on Sep 1, 2017in Nature Medicine 32.62
David Scott77
Estimated H-index: 77
,
Feng Zhang101
Estimated H-index: 101
Analysis of the ExAC and 1000 Genomes data sets estimates the impact of inter-individual variation on the efficacy and safety of therapies based on CRISPR endonucleases.
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Cited By1
Published on Jul 17, 2018in Pathology & Oncology Research 1.94
Xi-ping Zhang , Qi-hui Cheng + 1 AuthorsEnqi Qiao1
Estimated H-index: 1
With abilities to renew themselves and lead to heterogeneity of tumors, cancer stem cells (CSCs) are similar to stem cells. As three leading causes of death that endanger women’s health, breast cancer, ovarian cancer and cervical cancer are characterized by high degree of malignancy, metastasis and recurrence. Associated with women’s fertility, these three malignancies are common and representative among females. These years, research findings have suggested that CSCs are closely connected with ...
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