Edited course of biomedical research: leaping forward with CRISPR

Published on Nov 1, 2017in Pharmacological Research 4.90
· DOI :10.1016/j.phrs.2017.09.008
Patrick J. Collins2
Estimated H-index: 2
(Amgen),
Christopher M. Hale13
Estimated H-index: 13
(Amgen),
Han Xu1
Estimated H-index: 1
(Amgen)
Abstract
Abstract Within the short few years since the report of its application in precise genome editing, CRISPR technology has become the method of choice to modify and modulate gene expression in biomedical research and therapeutic development. Subsequently, a variety of research, diagnostic, and therapeutic tools have been developed based upon CRISPR’s mechanism of action. Such tools have helped to deepen the understanding of fundamental biology and broaden the horizon in the search for treatments for diseases that have been considered hard or impossible to cure. As CRISPR technology advances closer to clinical applications, its short comings are becoming more apparent, thus creating opportunities to improve the technology’s efficacy, specificity, and safety profile in this setting. We will summarize the current status of CRISPR technology and discuss its future impact in this review.
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References85
Published on Nov 27, 2015in Science 41.06
Tim Wang6
Estimated H-index: 6
,
Kivanc Birsoy29
Estimated H-index: 29
+ 5 AuthorsDavid M. Sabatini111
Estimated H-index: 111
Large-scale genetic analysis of lethal phenotypes has elucidated the molecular underpinnings of many biological processes. Using the bacterial clustered regularly interspaced short palindromic repeats (CRISPR) system, we constructed a genome-wide single-guide RNA library to screen for genes required for proliferation and survival in a human cancer cell line. Our screen revealed the set of cell-essential genes, which was validated with an orthogonal gene-trap–based screen and comparison with yeas...
427 Citations Source Cite
Published on Jan 3, 2014in Science 41.06
Ophir Shalem18
Estimated H-index: 18
(Broad Institute),
Neville E. Sanjana20
Estimated H-index: 20
(Broad Institute)
+ 8 AuthorsJohn G. Doench25
Estimated H-index: 25
(Broad Institute)
The simplicity of programming the CRISPR (clustered regularly interspaced short palindromic repeats)–associated nuclease Cas9 to modify specific genomic loci suggests a new way to interrogate gene function on a genome-wide scale. We show that lentiviral delivery of a genome-scale CRISPR-Cas9 knockout (GeCKO) library targeting 18,080 genes with 64,751 unique guide sequences enables both negative and positive selection screening in human cells. First, we used the GeCKO library to identify genes es...
1,738 Citations Source Cite
Published on Nov 1, 2013in Nature Biotechnology 35.72
Alexander Kamb1
Estimated H-index: 1
,
Sean Harper1
Estimated H-index: 1
,
Kari Stefansson159
Estimated H-index: 159
New technology has transformed human genetics. It now provides perhaps the single best opportunity to innovate and improve clinical success rates in drug development.
20 Citations Source Cite
Published on Dec 1, 2013in Nature Biotechnology 35.72
Morgan L. Maeder26
Estimated H-index: 26
,
James Angstman3
Estimated H-index: 3
+ 10 AuthorsBradley E. Bernstein77
Estimated H-index: 77
A fusion protein comprising a TALE DNA-targeting domain and the 5-methylcytosine hydroxylase TET1 enables investigation of the function of specific DNA methylation events.
280 Citations Source Cite
Published on Feb 15, 2013in Science 41.06
Prashant Mali28
Estimated H-index: 28
(Harvard University),
Luhan Yang16
Estimated H-index: 16
(Harvard University)
+ 5 AuthorsGeorge M Church G M132
Estimated H-index: 132
(Wyss Institute for Biologically Inspired Engineering)
Bacteria and archaea have evolved adaptive immune defenses, termed clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems, that use short RNA to direct degradation of foreign nucleic acids. Here, we engineer the type II bacterial CRISPR system to function with custom guide RNA (gRNA) in human cells. For the endogenous AAVS1 locus, we obtained targeting rates of 10 to 25% in 293T cells, 13 to 8% in K562 cells, and 2 to 4% in induced pluripotent stem cel...
4,240 Citations Source Cite
Published on Mar 1, 2014in Nature Methods 26.92
Yuichiro Miyaoka9
Estimated H-index: 9
,
Amanda H. Chan4
Estimated H-index: 4
+ 6 AuthorsBruce R. Conklin55
Estimated H-index: 55
(University of California, San Francisco)
Precise editing of human genomes in pluripotent stem cells by homology-driven repair of targeted nuclease-induced cleavage has been hindered by the difficulty of isolating rare clones. We developed an efficient method to capture rare mutational events, enabling isolation of mutant lines with single-base substitutions without antibiotic selection. This method facilitates efficient induction or reversion of mutations associated with human disease in isogenic human induced pluripotent stem cells.
102 Citations Source Cite
Published on Oct 1, 2015in Oncogene 6.85
Sabine Stolzenburg8
Estimated H-index: 8
,
Adriana S. Beltran17
Estimated H-index: 17
+ 3 AuthorsPilar Blancafort23
Estimated H-index: 23
With the recent comprehensive mapping of cancer genomes, there is now a need for functional approaches to edit the aberrant epigenetic state of key cancer drivers to reprogram the epi-pathology of the disease. In this study we utilized a programmable DNA-binding methyltransferase to induce targeted incorporation of DNA methylation (DNAme) in the SOX2 oncogene in breast cancer through a six zinc finger (ZF) protein linked to DNA methyltransferase 3A (ZF-DNMT3A). We demonstrated long-lasting oncog...
37 Citations Source Cite
Published on May 1, 2015in Nature Reviews Genetics 41.47
Ophir Shalem18
Estimated H-index: 18
,
Neville E. Sanjana20
Estimated H-index: 20
,
Feng Zhang101
Estimated H-index: 101
CRISPR–Cas9 has been adopted as a powerful genome-editing technology in various species. By generating libraries of thousands of guide RNAs — which direct the Cas9 nuclease to chosen genomic loci — high-throughput genetic perturbations are now possible. This Review discusses the latest applications of CRISPR–Cas9 in mammalian functional genomics screens. It covers related genome-scale applications of Cas9 for either gene knockout or transcriptional modulation, and provides comparisons with compl...
408 Citations Source Cite
Published on Dec 1, 2014in Nature 41.58
Mitchell R. O’Connell7
Estimated H-index: 7
,
Benjamin L. Oakes8
Estimated H-index: 8
+ 3 AuthorsJennifer A. Doudna90
Estimated H-index: 90
In the presence of a short DNA oligonucleotide containing a protospacer adjacent motif, a guide-RNA-programmed Cas9 is able to specifically bind and/or cleave single-stranded RNA—this system can be used to isolate specific endogenous RNA transcripts from a cell lysate without any tag or modification.
246 Citations Source Cite
Published on Dec 1, 2013in Nature Biotechnology 35.72
Eric M. Mendenhall12
Estimated H-index: 12
,
Kaylyn Williamson3
Estimated H-index: 3
+ 4 AuthorsBradley E. Bernstein77
Estimated H-index: 77
(Harvard University)
The function of specific enhancers is studied using TAL effectors fused to a histone demethylase.
252 Citations Source Cite
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Cited By3
Published on Sep 1, 2018in Developmental Biology 3.26
S. Morgani3
Estimated H-index: 3
(Medical Research Council),
Nestor Saiz9
Estimated H-index: 9
(Memorial Sloan Kettering Cancer Center)
+ 7 AuthorsAnna-Katerina Hadjantonakis53
Estimated H-index: 53
(Cornell University)
Abstract The FGF/ERK signaling pathway is highly conserved throughout evolution and plays fundamental roles during embryonic development and in adult organisms. While a plethora of expression data exists for ligands, receptors and pathway regulators, we know little about the spatial organization or dynamics of signaling in individual cells within populations. To this end we developed a transcriptional readout of FGF/ERK activity by targeting a histone H2B-linked Venus fluorophore to the endogeno...
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Published on Mar 1, 2019in Leukemia 10.02
Olivier Humbert5
Estimated H-index: 5
(Fred Hutchinson Cancer Research Center),
George S. Laszlo11
Estimated H-index: 11
(Fred Hutchinson Cancer Research Center)
+ 7 AuthorsRoland B. Walter37
Estimated H-index: 37
(University of Washington)
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