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Correction of a pathogenic gene mutation in human embryos

Published on Aug 1, 2017in Nature 41.58
· DOI :10.1038/nature23305
Hong Ma27
Estimated H-index: 27
(Oregon National Primate Research Center),
Nuria Marti-Gutierrez1
Estimated H-index: 1
(Oregon Health & Science University)
+ 28 AuthorsShoukhrat Mitalipov36
Estimated H-index: 36
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.
  • References (48)
  • Citations (259)
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...
80 Citations Source Cite
Published on Feb 1, 2017in Scientific Reports 4.12
Zhuchi Tu7
Estimated H-index: 7
Weili Yang9
Estimated H-index: 9
+ 10 AuthorsSu Yang9
Estimated H-index: 9
20 Citations Source Cite
Published on Jan 15, 2017in Bioinformatics 5.48
Jeongbin Park8
Estimated H-index: 8
(Hanyang University),
Kayeong Lim4
Estimated H-index: 4
(Seoul National University)
+ 1 AuthorsSangsu Bae13
Estimated H-index: 13
(Hanyang University)
43 Citations Source Cite
Published on Oct 1, 2016in Developmental Biology 3.26
Masakazu Hashimoto7
Estimated H-index: 7
(Osaka University),
Yukiko Yamashita2
Estimated H-index: 2
(University of Tokushima),
Tatsuya Takemoto13
Estimated H-index: 13
(University of Tokushima)
Abstract The CRISPR/Cas9 system is a powerful tool for elucidating the roles of genes in a wide variety of organisms including mice. To obtain genetically modified embryos or mice by this method, Cas9 mRNA and sgRNA are usually introduced into zygotes by microinjection or electroporation. However, most mutants generated with this method are genetically mosaic, composed of several types of cells carrying different mutations, which complicates phenotype analysis in founder embryos or mice. To simp...
47 Citations Source Cite
Published on Oct 1, 2016in Cell 31.40
Julian Lange12
Estimated H-index: 12
(Memorial Sloan Kettering Cancer Center),
Shintaro Yamada3
Estimated H-index: 3
(Memorial Sloan Kettering Cancer Center)
+ 6 AuthorsScott Keeney47
Estimated H-index: 47
(Cornell University)
Summary Heritability and genome stability are shaped by meiotic recombination, which is initiated via hundreds of DNA double-strand breaks (DSBs). The distribution of DSBs throughout the genome is not random, but mechanisms molding this landscape remain poorly understood. Here, we exploit genome-wide maps of mouse DSBs at unprecedented nucleotide resolution to uncover previously invisible spatial features of recombination. At fine scale, we reveal a stereotyped hotspot structure—DSBs occur withi...
64 Citations Source Cite
Published on May 1, 2016in Cell Stem Cell 23.29
Eunju Kang13
Estimated H-index: 13
(Oregon National Primate Research Center),
Xinjian Wang20
Estimated H-index: 20
(Cincinnati Children's Hospital Medical Center)
+ 20 AuthorsYing Li14
Estimated H-index: 14
(Oregon National Primate Research Center)
Summary The genetic integrity of iPSCs is an important consideration for therapeutic application. In this study, we examine the accumulation of somatic mitochondrial genome (mtDNA) mutations in skin fibroblasts, blood, and iPSCs derived from young and elderly subjects (24–72 years). We found that pooled skin and blood mtDNA contained low heteroplasmic point mutations, but a panel of ten individual iPSC lines from each tissue or clonally expanded fibroblasts carried an elevated load of heteroplas...
76 Citations Source Cite
Published on Mar 1, 2016in Nature Biotechnology 35.72
Christopher D. Richardson27
Estimated H-index: 27
Graham Jordan Ray4
Estimated H-index: 4
+ 2 AuthorsJacob E. Corn29
Estimated H-index: 29
The efficiency of homology-directed genome editing with CRISPR-Cas9 is boosted through improved design of donor DNA.
306 Citations Source Cite
Published on Mar 1, 2016in Genome Research 10.10
Daesik Kim12
Estimated H-index: 12
(Seoul National University),
Sojung Kim10
Estimated H-index: 10
(Seoul National University)
+ 2 AuthorsJin-Soo Kim52
Estimated H-index: 52
(Seoul National University)
We present multiplex Digenome-seq to profile genome-wide specificities of up to 11 CRISPR-Cas9 nucleases simultaneously, saving time and reducing cost. Cell-free human genomic DNA was digested using multiple sgRNAs combined with the Cas9 protein and then subjected to whole-genome sequencing. In vitro cleavage patterns, characteristic of on- and off-target sites, were computationally identified across the genome using a new DNA cleavage scoring system. We found that many false-positive, bulge-typ...
75 Citations Source Cite
Published on Dec 20, 2015in Human Molecular Genetics 4.90
Yu Kang8
Estimated H-index: 8
(Kunming University),
Bo Zheng8
Estimated H-index: 8
(Nanjing Medical University)
+ 13 AuthorsHong Wang9
Estimated H-index: 9
(Kunming University)
Mutations in the DAX1 locus cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH), which manifest with primary adrenal insufficiency and incomplete or absent sexual maturation, respectively. The associated defects in spermatogenesis can range from spermatogenic arrest to Sertoli cell only syndrome. Conclusions from Dax1 knockout mouse models provide only limited insight into AHC/HH disease mechanisms, because mouse models exhibit more extensive abnormalities in...
36 Citations Source Cite
Published on Dec 1, 2015in Gene 2.50
Lucie Carrier43
Estimated H-index: 43
(University of Hamburg),
Giulia Mearini16
Estimated H-index: 16
(University of Hamburg)
+ 1 AuthorsFriederike Cuello6
Estimated H-index: 6
(University of Hamburg)
Abstract More than 350 individual MYPBC3 mutations have been identified in patients with inherited hypertrophic cardiomyopathy (HCM), thus representing 40–50% of all HCM mutations, making it the most frequently mutated gene in HCM. HCM is considered a disease of the sarcomere and is characterized by left ventricular hypertrophy, myocyte disarray and diastolic dysfunction. MYBPC3 encodes for the thick filament associated protein cardiac myosin-binding protein C (cMyBP-C), a signaling node in card...
46 Citations Source Cite
Cited By259
Published on Jan 8, 2019in Nature Communications 12.35
Puping Liang7
Estimated H-index: 7
(Sun Yat-sen University),
Xiaowei Xie6
Estimated H-index: 6
(Sun Yat-sen University)
+ 9 AuthorsDan Liu26
Estimated H-index: 26
(Baylor College of Medicine)
The adenine base editor (ABE), capable of catalyzing A•T to G•C conversions, is an important gene editing toolbox. Here, we systematically evaluate genome-wide off-target deamination by ABEs using the EndoV-seq platform we developed. EndoV-seq utilizes Endonuclease V to nick the inosine-containing DNA strand of genomic DNA deaminated by ABE in vitro. The treated DNA is then whole-genome sequenced to identify off-target sites. Of the eight gRNAs we tested with ABE, 2–19 (with an average of 8.0) o...
7 Citations Source Cite
Published on Jun 3, 2019in Nature Medicine 32.62
Source Cite
Published on Jan 23, 2019
Some authors have proposed that research on cognitive differences is too dangerous to be allowed to proceed unchecked. From a consequentialist perspective, this contribution investigates the usually unstated assumptions about harms and benefits behind these proposals, finding that knowledge about intelligence differences is not always more harmful than alternative false beliefs. The main conclusion is that the proper questions to ask are not about the nature of the research, but about whether pr...
Bruno Kotska Rodiño-Janeiro5
Estimated H-index: 5
(Autonomous University of Barcelona),
Cristina Pardo-Camacho3
Estimated H-index: 3
(Autonomous University of Barcelona)
+ 1 AuthorsCristina Martinez12
Estimated H-index: 12
(Autonomous University of Barcelona)
Irritable bowel syndrome (IBS) is one of the commonest gastrointestinal disorders. Although long-time considered a pure functional disorder, intense research in past years has rendered a very compl...
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Published on Jun 1, 2019in Pharmaceutical medicine
François Hirsch23
Estimated H-index: 23
(French Institute of Health and Medical Research),
Christine Lemaitre (French Institute of Health and Medical Research)+ 1 AuthorsLluís Montoliu33
Estimated H-index: 33
(Spanish National Research Council)
For more than 40 years, scientists have been developing tools and technologies for genome modification; however, initial progress was slow and few outside of the molecular biology community took an interest in the field. Everything has dramatically changed with the recent appearance of the so-called precision approaches, and especially with the ‘CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) revolution’. With great powers come great responsibilities. CRISPR-derived technologie...
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Liting You1
Estimated H-index: 1
(Sichuan University),
Ruizhan Tong2
Estimated H-index: 2
(Sichuan University)
+ 3 AuthorsYou Lu24
Estimated H-index: 24
(Sichuan University)
The expanding CRISPR-Cas9 technology is an easily accessible, programmable, and precise gene-editing tool with numerous applications, most notably in biomedical research. Together with advancements in genome and transcriptome sequencing in the era of metadata, genomic engineering with CRISPR-Cas9 meets the developmental requirements of precision medicine, and clinical tests using CRISPR-Cas9 are now possible. This review summarizes developments and established preclinical applications of CRISPR-...
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Published on May 24, 2019in Circulation Research 15.21
Giuliana G. Repetti2
Estimated H-index: 2
(Harvard University),
Christopher N. Toepfer5
Estimated H-index: 5
(University of Oxford)
+ 1 AuthorsChristine E. Seidman115
Estimated H-index: 115
(Harvard University)
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