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  • Citations (20)
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 Jun 7, 2016in Frontiers in Genetics 4.15
Shane M. Harding13
Estimated H-index: 13
(UPenn: University of Pennsylvania),
Roger A. Greenberg37
Estimated H-index: 37
(UPenn: University of Pennsylvania)
The cellular response to DNA double strand breaks (DSBs) is a multifaceted signaling program that centers on post-translational modifications including phosphorylation, ubiquitylation and SUMOylation. In this review we discuss how ubiquitin and SUMO orchestrate the recognition of DSBs and explore how this influences chromatin organization. We discuss functional outcomes of this response including transcriptional silencing and how pre-existing chromatin states may control the DSB response and the...
9 Citations Source Cite
Published on Jun 1, 2016in Development 5.41
Alexa Burger7
Estimated H-index: 7
(UZH: University of Zurich),
Helen Lindsay12
Estimated H-index: 12
(Swiss Institute of Bioinformatics)
+ 9 AuthorsMartin Jinek26
Estimated H-index: 26
(UZH: University of Zurich)
CRISPR-Cas9 enables efficient sequence-specific mutagenesis for creating somatic or germline mutants of model organisms. Key constraints in vivo remain the expression and delivery of active Cas9-guideRNA ribonucleoprotein complexes (RNPs) with minimal toxicity, variable mutagenesis efficiencies depending on targeting sequence, and high mutation mosaicism. Here, we apply in vitro -assembled, fluorescent Cas9-sgRNA RNPs in solubilizing salt solution to achieve maximal mutagenesis efficiency in zeb...
66 Citations Source Cite
Published on Apr 1, 2016in Nature Communications 12.35
Jun Song6
Estimated H-index: 6
(UM: University of Michigan),
Dongshan Yang7
Estimated H-index: 7
+ 3 AuthorsJifeng Zhang41
Estimated H-index: 41
(UM: University of Michigan)
Zinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will imp...
118 Citations Source Cite
Published on Feb 1, 2016in Nature Biotechnology 35.72
John G. Doench26
Estimated H-index: 26
Nicolo Fusi12
Estimated H-index: 12
+ 10 AuthorsRobert C. Orchard12
Estimated H-index: 12
Genome-wide sgRNA libraries based on rules for on-target activity improve results of Cas9-based screens and facilitate a further refinement of on- and off-target prediction algorithms.
560 Citations Source Cite
Published on Feb 1, 2016in Scientific Reports 4.12
Lin Yuan6
Estimated H-index: 6
Tingting Sui5
Estimated H-index: 5
+ 7 AuthorsLiangxue Lai44
Estimated H-index: 44
Cataracts are the leading cause of vision loss in the world, although surgical treatment can restore vision in cataract patients. Until now, there have been no adequate animal models for in vivo studies of artificial lens safety and drug interactions. Genetic studies have demonstrated that GJA8 is involved in maintaining lens opacity and proper lens development. In this study, a cataract model with GJA8 gene knockout was developed via co-injection of Cas9/sgRNA mRNA into rabbit zygotes. Our resu...
20 Citations Source Cite
Published on Feb 1, 2016in Cell 31.40
Krishnaraj Rajalingam24
Estimated H-index: 24
Ivan Dikic89
Estimated H-index: 89
(Goethe University Frankfurt)
The Ubiquitin (Ub) system coordinates vital cellular processes by controlling lifetime, signaling, and binding properties of proteins. Ub serves as a multivalent protein tag that is further diversified by post-translational modifications. Specialized Ub receptors then convert the encoded signals into cellular responses. This SnapShot highlights the importance of the rapidly expanding Ub code in biology as well as novel pharmacological approaches to target the Ub system in multiple diseases. To v...
15 Citations Source Cite
Published on Jan 1, 2016in Nature 41.58
Benjamin P. Kleinstiver12
Estimated H-index: 12
(Harvard University),
Vikram Pattanayak11
Estimated H-index: 11
(Harvard University)
+ 4 AuthorsJ. Keith Joung60
Estimated H-index: 60
(Harvard University)
A high-fidelity variant of Streptococcus pyogenes CRISPR–Cas9 is reported that lacks detectable off-target events as assessed by genome-wide break capture and targeted sequencing methods.
797 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 Journal of Molecular Cell Biology 5.59
Qingjian Zou9
Estimated H-index: 9
(Guangzhou Institutes of Biomedicine and Health),
Xiaomin Wang2
Estimated H-index: 2
(NU: Nanjing University)
+ 25 AuthorsJun Shen1
Estimated H-index: 1
(SYSU: Sun Yat-sen University)
45 Citations Source Cite
Cited By20
Published on Dec 1, 2019in Scientific Reports 4.12
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Published on Jun 3, 2019in Nature Medicine 32.62
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Published on Jan 31, 2019in National Science Review 9.41
Jianguo Zhao (CAS: Chinese Academy of Sciences), Liangxue Lai (Guangzhou Institutes of Biomedicine and Health)+ 1 AuthorsQi Zhou51
Estimated H-index: 51
(CAS: Chinese Academy of Sciences)
Source Cite
Published on May 1, 2019in Cell 31.40
Basudeb Maji1
Estimated H-index: 1
(Broad Institute),
Soumyashree A. Gangopadhyay1
Estimated H-index: 1
(Broad Institute)
+ 15 AuthorsBishwajit Paul1
Estimated H-index: 1
(Broad Institute)
Summary The precise control of CRISPR-Cas9 activity is required for a number of genome engineering technologies. Here, we report a generalizable platform that provided the first synthetic small-molecule inhibitors of Streptococcus pyogenes Cas9 (SpCas9) that weigh
1 Citations Source Cite
Published on Mar 1, 2019in Reproduction in Domestic Animals 1.42
Yongjie Wan8
Estimated H-index: 8
(NAU: Nanjing Agricultural University),
Rihong Guo2
Estimated H-index: 2
(Ministry of Science and Technology)
+ 5 AuthorsFeng Wang16
Estimated H-index: 16
(NAU: Nanjing Agricultural University)
Source Cite
Published on Jan 1, 2019in Developmental Biology 3.26
Maryam Mehravar1
Estimated H-index: 1
(Avicenna Research Institute),
Abolfazl Shirazi13
Estimated H-index: 13
(Shahrekord University)
+ 1 AuthorsMehdi Banan9
Estimated H-index: 9
Abstract The CRISPR/Cas9 system is a rapid, simple, and often extremely efficient gene editing method. This method has been used in a variety of organisms and cell types over the past several years. However, using this technology for generating gene-edited animals involves a number of obstacles. One such obstacle is mosaicism, which is common in founder animals. This is especially the case when the CRISPR/Cas9 system is used in embryos. Here we review the pros and cons of mosaic mutations of gen...
3 Citations Source Cite
Published on Jan 1, 2019in Journal of Molecular Biology 4.89
Carolyn Brokowski1
Estimated H-index: 1
(Yale University),
Mazhar Adli25
Estimated H-index: 25
(UVA: University of Virginia)
Abstract With the emergence of CRISPR technology, targeted editing of a wide variety of genomes is no longer an abstract hypothetical, but occurs regularly. As application areas of CRISPR are exceeding beyond research and biomedical therapies, new and existing ethical concerns abound throughout the global community about the appropriate scope of the systems' use. Here we review fundamental ethical issues including the following: 1) the extent to which CRISPR use should be permitted; 2) access to...
2 Citations Source Cite
Published on Dec 1, 2018in Cell Reports 8.03
Su Yang9
Estimated H-index: 9
(Emory University),
Li Shihua76
Estimated H-index: 76
(Emory University),
Xiao-Jiang Li61
Estimated H-index: 61
(Emory University)
Summary Virus-mediated expression of CRISPR/Cas9 is commonly used for genome editing in animal brains to model or treat neurological diseases, but the potential neurotoxicity of overexpressing bacterial Cas9 in the mammalian brain remains unknown. Through RNA sequencing (RNA-seq) analysis, we find that virus-mediated expression of Cas9 influences the expression of genes involved in neuronal functions. Reducing the half-life of Cas9 by tagging with geminin, whose expression is regulated by the ce...
2 Citations Source Cite
Published on Dec 1, 2018in Transgenic Research 2.20
Marcela Vilarino4
Estimated H-index: 4
(UC Davis: University of California, Davis),
Fabian Suchy5
Estimated H-index: 5
(Stanford University)
+ 7 AuthorsPablo J. Ross21
Estimated H-index: 21
(UC Davis: University of California, Davis)
The production of knock-out (KO) livestock models is both expensive and time consuming due to their long gestational interval and low number of offspring. One alternative to increase efficiency is performing a genetic screening to select pre-implantation embryos that have incorporated the desired mutation. Here we report the use of sheep embryo biopsies for detecting CRISPR/Cas9-induced mutations targeting the gene PDX1 prior to embryo transfer. PDX1 is a critical gene for pancreas development a...
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