The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells
Open accessAbstract
Bacterial type II CRISPR-Cas9 systems have been widely adapted for RNA-guided genome editing and transcription regulation in eukaryotic cells, yet their in vivo target specificity is poorly understood. Here we mapped genome-wide binding sites of a catalytically inactive Cas9 (dCas9) from Streptococcus pyogenes loaded with single guide RNAs (sgRNAs) in mouse embryonic stem cells (mESCs). Each of the four sgRNAs we tested targets dCas9 to between tens and thousands of genomic sites, frequently characterized by a 5-nucleotide seed region in the sgRNA and an NGG protospacer adjacent motif (PAM). Chromatin inaccessibility decreases dCas9 binding to other sites with matching seed sequences; thus 70% of off-target sites are associated with genes. Targeted sequencing of 295 dCas9 binding sites in mESCs transfected with catalytically active Cas9 identified only one site mutated above background levels. We propose a two-state model for Cas9 binding and cleavage, in which a seed match triggers binding but extensive pairing with target DNA is required for cleavage.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“| Delivery methods improvement | Application in cell culture [89–94] | Viral transduction | May cause accumulation of off-target mutations |”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as [93]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“| Delivery methods improvement | Application in cell culture [89–94] | Plasmid transfection | May cause accumulation of off-target mutations |”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as [93]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“| Delivery methods improvement | Application in cell culture [89–94] | RNP electroporation: Rapid transfection and turnover | Eliminate off-target effects |”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as [93]
Experimental — accuracy not yet measuredIn the citing paper
“A key feature of our system is the transient expression of the nuclease Cas9, through delivery of mRNA. This allowed for sufficient exposure to the nuclease for gene repair and reduced concerns associated with long-term nuclease exposure34.”
From Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo (2016) · cites this paper as [34]
In the citing paper
“And moreover, DNA binding and cleavage by Cas9 are in some cases uncoupled, that is, Cas9 can bind to but not cleave DNA sequences that are partially complementary to sgRNA 49 and exert epigenomic regulatory effects, 43 44 which is unpredictable by silicon methods relying on base pairing.”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [49]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012) · Science · doi:10.1126/science.1225829 · Cited by 17,116
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339
Self-citationWebLogo: A Sequence Logo Generator: Figure 1Preprint
Crooks, G. E., Hon, G. C., Chandonia, J., & Brenner, S. E. (2004) · Genome Research · doi:10.1101/gr.849004 · Cited by 12,480
RNA-Guided Human Genome Engineering via Cas9
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210
Genome-scale CRISPR-Cas9 knockout screening in human cells
Shalem, O., Sanjana, N. E., Hartenian, E., Shi, X., Scott, D. A., Mikkelsen, T. S., Heckl, D., Ebert, B. L., Root, D. E., Doench, J. G., et al. (2014) · Science · doi:10.1126/science.1247005 · Cited by 5,234
Self-citationRepurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression
Qi, L. S., Larson, M. H., Gilbert, L. A., Doudna, J. A., Weissman, J. S., Arkin, A. P., & Lim, W. A. (2013) · Cell · doi:10.1016/j.cell.2013.02.022 · Cited by 5,016
DNA targeting specificity of RNA-guided Cas9 nucleases
Hsu, P. D., Scott, D. A., Weinstein, J. A., Ran, F. A., Konermann, S., Agarwala, V., Li, Y., Fine, E. J., Wu, X., Shalem, O., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2647 · Cited by 4,741
Cited by
Sorted by citations
The new frontier of genome engineering with CRISPR-Cas9
Doudna, J. A., & Charpentier, E. (2014) · Science · doi:10.1126/science.1258096 · Cited by 7,062
Development and Applications of CRISPR-Cas9 for Genome Engineering
Hsu, P. D., Lander, E. S., & Zhang, F. (2014) · Cell · doi:10.1016/j.cell.2014.05.010 · Cited by 5,762
Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex
Konermann, S., Brigham, M. D., Trevino, A. E., Joung, J., Abudayyeh, O. O., Barcena, C., Hsu, P. D., Habib, N., Gootenberg, J. S., Nishimasu, H., et al. (2015) · Nature · doi:10.1038/nature14136 · Cited by 2,825
Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation
Gilbert, L. A., Horlbeck, M. A., Adamson, B., Villalta, J. E., Chen, Y., Whitehead, E. H., Guimaraes, C., Panning, B., Ploegh, H. L., Bassik, M. C., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.029 · Cited by 2,728
In vivo genome editing using Staphylococcus aureus Cas9
Ran, F. A., Cong, L., Yan, W. X., Scott, D. A., Gootenberg, J. S., Kriz, A. J., Zetsche, B., Shalem, O., Wu, X., Makarova, K. S., et al. (2015) · Nature · doi:10.1038/nature14299 · Cited by 2,687
Self-citationGUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases
Tsai, S. Q., Zheng, Z., Nguyen, N. T., Liebers, M., Topkar, V. V., Thapar, V., Wyvekens, N., Khayter, C., Iafrate, A. J., Le, L. P., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3117 · Cited by 2,268
CRISPR–Cas9 Structures and Mechanisms
Jiang, F., & Doudna, J. A. (2017) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-062215-010822 · Cited by 2,029
Hilton, I. B., D’Ippolito, A. M., Vockley, C. M., Thakore, P. I., Crawford, G. E., Reddy, T. E., & Gersbach, C. A. (2015) · Nature Biotechnology · doi:10.1038/nbt.3199 · Cited by 1,931
The CRISPR tool kit for genome editing and beyond
Adli, M. (2018) · Nature Communications · doi:10.1038/s41467-018-04252-2 · Cited by 1,545
Rational design of highly active sgRNAs for CRISPR-Cas9-mediated gene inactivation
Doench, J. G., Hartenian, E., Graham, D. B., Tothova, Z., Hegde, M., Smith, I., Sullender, M., Ebert, B. L., Xavier, R. J., & Root, D. E. (2014) · Nature Biotechnology · doi:10.1038/nbt.3026 · Cited by 1,617
Off-target Effects in CRISPR/Cas9-mediated Genome Engineering
Zhang, X.-H., Tee, L. Y., Wang, X.-G., Huang, Q.-S., & Yang, S.-H. (2015) · Molecular Therapy - Nucleic Acids · doi:10.1038/mtna.2015.37 · Cited by 1,273
Editing DNA Methylation in the Mammalian Genome
Liu, X. S., Wu, H., Ji, X., Stelzer, Y., Wu, X., Czauderna, S., Shu, J., Dadon, D., Young, R. A., & Jaenisch, R. (2016) · Cell · doi:10.1016/j.cell.2016.08.056 · Cited by 1,224
High-throughput functional genomics using CRISPR-Cas9
Shalem, O., Sanjana, N. E., & Zhang, F. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3899 · Cited by 1,233
Self-citationCRISPR/Cas9 in Genome Editing and Beyond
Wang, H., Russa, M. F. L., & Qi, L. S. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014607 · Cited by 1,213
CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes
Liang, P., Xu, Y., Zhang, X., Ding, C., Huang, R., Zhang, Z., Lv, J., Xie, X., Chen, Y., Li, Y., et al. (2015) · Protein & Cell · doi:10.1007/s13238-015-0153-5 · Cited by 1,135
Thakore, P. I., D'Ippolito, A. M., Song, L., Safi, A., Shivakumar, N. K., Kabadi, A. M., Reddy, T. E., Crawford, G. E., & Gersbach, C. A. (2015) · Nature Methods · doi:10.1038/nmeth.3630 · Cited by 1,012
Digenome-seq: Genome-wide profiling of CRISPR-cas9 off-target effects in human cells
Kim, D., Bae, S., Park, J., Kim, E., Kim, S., Yu, H. R., Hwang, J., Kim, J.-I., & Kim, J.-S. (2015) · Nature Methods · doi:10.1038/nmeth.3284 · Cited by 992
CRISPR-Based Technologies for the Manipulation of Eukaryotic Genomes
Komor, A. C., Badran, A. H., & Liu, D. R. (2016) · Cell · doi:10.1016/j.cell.2016.10.044 · Cited by 1,037
Yin, H., Song, C.-Q., Dorkin, J. R., Zhu, L. J., Li, Y., Wu, Q., Park, A., Yang, J., Suresh, S., Bizhanova, A., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3471 · Cited by 876
Beyond editing: repurposing CRISPR-Cas9 for precision genome regulation and interrogation
Dominguez, A. A., Lim, W. A., & Qi, L. S. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.2 · Cited by 832
Guilinger, J. P., Thompson, D. B., & Liu, D. R. (2014) · Nature Biotechnology · doi:10.1038/nbt.2909 · Cited by 836
Prevention of muscular dystrophy in mice by CRISPR/Cas9–mediated editing of germline DNA
Long, C., McAnally, J. R., Shelton, J. M., Mireault, A. A., Bassel-Duby, R., & Olson, E. N. (2014) · Science · doi:10.1126/science.1254445 · Cited by 720
Genome-editing Technologies for Gene and Cell Therapy
Maeder, M. L., & Gersbach, C. A. (2016) · Molecular Therapy · doi:10.1038/mt.2016.10 · Cited by 736
Conformational control of DNA target cleavage by CRISPR–Cas9
Sternberg, S. H., LaFrance, B., Kaplan, M., & Doudna, J. A. (2015) · Nature · doi:10.1038/nature15544 · Cited by 627
Sequence determinants of improved CRISPR sgRNA design
Xu, H., Xiao, T., Chen, C.-H., Li, W., Meyer, C. A., Wu, Q., Wu, D., Cong, L., Zhang, F., Liu, J. S., et al. (2015) · Genome Research · doi:10.1101/gr.191452.115 · Cited by 625
Off-target effects in CRISPR/Cas9 gene editing
Guo, C., Ma, X., Gao, F., & Guo, Y. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1143157 · Cited by 704
“This method uses catalytically inactive Cas9 (dCas9), which can bind to genome DNA without introducing DSBs and detaching from the edited sites (Kuscu et al., 2014; Wu et al., 2014).”
MethodPast, present, and future of CRISPR genome editing technologies
Pacesa, M., Pelea, O., & Jinek, M. (2024) · Cell · doi:10.1016/j.cell.2024.01.042 · Cited by 609
Hurtado, S., Milem, J. F., Clayton-Pedersen, A. R., & Allen, W. R. (1999) · Cited by 568
A Cas9–guide RNA complex preorganized for target DNA recognition
Jiang, F., Zhou, K., Ma, L., Gressel, S., & Doudna, J. A. (2015) · Science · doi:10.1126/science.aab1452 · Cited by 562
Wang, H.-X., Li, M., Lee, C. M., Chakraborty, S., Kim, H.-W., Bao, G., & Leong, K. W. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00799 · Cited by 560
Editing plant genomes with CRISPR/Cas9
Belhaj, K., Chaparro‐Garcia, A., Kamoun, S., Patron, N. J., & Nekrasov, V. (2014) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2014.11.007 · Cited by 559
Induced Pluripotent Stem Cells Meet Genome Editing
Hockemeyer, D., & Jaenisch, R. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.04.013 · Cited by 499
“…(Chen et al., 2015; Cong et al., 2013; Fu et al., 2014; Gonzalez et al., 2014; Gu et al., 2015; Hou et al., 2013; Hsu et al., 2014; Kleinstiver et al., 2016; Liao and Karnik, 2015; Lin et al., 2014; Mali et al., 2013; Ran et al., 2015; Slaymaker et al., 2016; Tsai et al., 2014; Wu et al., 2014b).”
BackgroundComparison of Cas9 activators in multiple species
Chavez, A., Tuttle, M. L., Pruitt, B. W., Ewen‐Campen, B., Chari, R., Ter‐Ovanesyan, D., Haque, S. J., Cecchi, R. J., Kowal, E. J. K., Buchthal, J., et al. (2016) · Nature Methods · doi:10.1038/nmeth.3871 · Cited by 521
Choosing the Right Tool for the Job: RNAi, TALEN, or CRISPR
Boettcher, M., & McManus, M. T. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.04.028 · Cited by 539
Defining and improving the genome-wide specificities of CRISPR–Cas9 nucleases
Tsai, S. Q., & Joung, J. K. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.28 · Cited by 523
Quality control, modeling, and visualization of CRISPR screens with MAGeCK-VISPR
Li, W., Köster, J., Xu, H., Chen, C.-H., Xiao, T., Liu, J. S., Brown, M. A., & Liu, X. S. (2015) · Genome biology · doi:10.1186/s13059-015-0843-6 · Cited by 503
An enhanced CRISPR repressor for targeted mammalian gene regulation
Yeo, N. C., Chavez, A., Lance‐Byrne, A., Chan, Y., Menn, D. J., Milanova, D., Kuo, C., Guo, X., Sharma, S., Tung, A., et al. (2018) · Nature Methods · doi:10.1038/s41592-018-0048-5 · Cited by 489
Inducible in vivo genome editing with CRISPR-Cas9
Dow, L. E., Fisher, J., O’Rourke, K. P., Muley, A., Kastenhuber, E. R., Livshits, G., Tschaharganeh, D. F., Socci, N. D., & Lowe, S. W. (2015) · Nature Biotechnology · doi:10.1038/nbt.3155 · Cited by 496
Efficient ablation of genes in human hematopoietic stem and effector cells using CRISPR/Cas9
Mandal, P. K., Ferreira, L. M. R., Collins, R., Meissner, T. B., Boutwell, C. L., Friesen, M., Vrbanac, V., Garrison, B. S., Stortchevoi, A., Bryder, D., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.10.004 · Cited by 475
“studies showing that mismatches in the 5′ end of the gRNA are tolerated by Cas9 (Lin et al., 2014; Wu et al., 2014).”
Latest Developed Strategies to Minimize the Off-Target Effects in CRISPR-Cas-Mediated Genome Editing
Naeem, M., Majeed, S., Hoque, M. Z., & Ahmad, I. (2020) · Cells · doi:10.3390/cells9071608 · Cited by 457
Editing the epigenome: technologies for programmable transcription and epigenetic modulation
Thakore, P. I., Black, J. B., Hilton, I. B., & Gersbach, C. A. (2016) · Nature Methods · doi:10.1038/nmeth.3733 · Cited by 451
Unbiased detection of CRISPR off-targets in vivo using DISCOVER-Seq
Wienert, B., Wyman, S. K., Richardson, C. D., Yeh, C. D., Akcakaya, P., Porritt, M. J., Morlock, M., Vu, J. T., Kazane, K. R., Watry, H. L., et al. (2019) · Science · doi:10.1126/science.aav9023 · Cited by 434
Nucleosomes impede Cas9 access to DNA in vivo and in vitro
Horlbeck, M. A., Witkowsky, L. B., Guglielmi, B., Replogle, J. M., Gilbert, L. A., Villalta, J. E., Torigoe, S. E., Tjian, R., & Weissman, J. S. (2016) · eLife · doi:10.7554/elife.12677 · Cited by 429
Rapid modelling of cooperating genetic events in cancer through somatic genome editing
Rivera, F. J. S., Papagiannakopoulos, T. Y., Romero, R., Tammela, T., Bauer, M. R., Bhutkar, A. J., Joshi, N. S., Subbaraj, L., Bronson, R. T., Xue, W., et al. (2014) · Nature · doi:10.1038/nature13906 · Cited by 413
Genome Engineering with CRISPR-Cas9 in the Mosquito Aedes aegypti
Kistler, K. E., Vosshall, L. B., & Matthews, B. J. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.009 · Cited by 417
Expanding the Biologist’s Toolkit with CRISPR-Cas9
Sternberg, S. H., & Doudna, J. A. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.02.032 · Cited by 409
Unraveling CRISPR-Cas9 genome engineering parameters via a library-on-library approach
Chari, R., Mali, P., Moosburner, M., & Church, G. M. (2015) · Nature Methods · doi:10.1038/nmeth.3473 · Cited by 404
Increasing the specificity of CRISPR systems with engineered RNA secondary structures
Kocak, D. D., Josephs, E. A., Bhandarkar, V., Adkar, S. S., Kwon, J. B., & Gersbach, C. A. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0095-1 · Cited by 351
WU-CRISPR: characteristics of functional guide RNAs for the CRISPR/Cas9 system
Wong, N. W., Liu, W., & Wang, X. (2015) · Genome biology · doi:10.1186/s13059-015-0784-0 · Cited by 383
Targeted mutagenesis in soybean using the CRISPR-Cas9 system
Sun, X., Hu, Z., Chen, R., Jiang, Q., Song, G., Zhang, H., & Xi, Y. (2015) · Scientific Reports · doi:10.1038/srep10342 · Cited by 384
Target specificity of the CRISPR‐Cas9 system
Wu, X., Kriz, A. J., & Sharp, P. A. (2014) · Quantitative Biology · doi:10.1007/s40484-014-0030-x · Cited by 388
Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens
Morgens, D. W., Wainberg, M., Boyle, E. A., Ursu, O., Araya, C. L., Tsui, C. K., Haney, M. S., Hess, G. T., Han, K., Jeng, E. E., et al. (2017) · Nature Communications · doi:10.1038/ncomms15178 · Cited by 362
Dynamics of CRISPR-Cas9 genome interrogation in living cells
Knight, S. C., Xie, L., Deng, W., Guglielmi, B., Witkowsky, L. B., Bosanac, L., Zhang, E., Beheiry, M. E., Masson, J., Dahan, M., et al. (2015) · Science · doi:10.1126/science.aac6572 · Cited by 362
Disabling Cas9 by an anti-CRISPR DNA mimic
Shin, J. J., Jiang, F., Liu, J., Bray, N., Rauch, B. J., Baik, R., Nogales, E., Bondy‐Denomy, J., Corn, J. E., & Doudna, J. A. (2017) · Science Advances · doi:10.1126/sciadv.1701620 · Cited by 358
An Agrobacterium‐delivered CRISPR /Cas9 system for high‐frequency targeted mutagenesis in maize
Char, S. N., Neelakandan, A. K., Nahampun, H. N., Frame, B. R., Main, M., Spalding, M. H., Becraft, P. W., Meyers, B. C., Walbot, V., Wang, K., et al. (2016) · Plant Biotechnology Journal · doi:10.1111/pbi.12611 · Cited by 352
Canver, M. C., Bauer, D. E., Dass, A., Yien, Y. Y., Chung, J., Masuda, T., Maeda, T., Paw, B. H., & Orkin, S. H. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.564625 · Cited by 357
Optimized CRISPR guide RNA design for two high-fidelity Cas9 variants by deep learning
Wang, D., Zhang, C., Wang, B., Li, B., Wang, Q., Liu, D., Wang, H., Zhou, Y., Shi, L., Lan, F., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12281-8 · Cited by 331
RNAi screening comes of age: improved techniques and complementary approaches
Mohr, S. E., Smith, J. A., Shamu, C. E., Neumüller, R. A., & Perrimon, N. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3860 · Cited by 344
CRISPR-Based Methods for Caenorhabditis elegans Genome Engineering
Dickinson, D. J., & Goldstein, B. (2016) · Genetics · doi:10.1534/genetics.115.182162 · Cited by 317
Wang, R., Zhao, X., Chen, X., Qiu, X., Qing, G., Zhang, H., Zhang, L., Hu, X., He, Z., Zhong, D., et al. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b04814 · Cited by 315
Ren, X., Yang, Z., Jiang, X., Sun, J., Mao, D., Hu, Y., Yang, S., Qiao, H., Wang, X., Hu, Q., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.09.044 · Cited by 310
A Mouse Geneticist’s Practical Guide to CRISPR Applications
Singh, P., Schimenti, J. C., & Bolcun‐Filas, E. (2014) · Genetics · doi:10.1534/genetics.114.169771 · Cited by 312
Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity
Tycko, J., Myer, V. E., & Hsu, P. D. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.07.004 · Cited by 315
Post-translational Regulation of Cas9 during G1 Enhances Homology-Directed Repair
Gutschner, T., Hämmerle, M., Genovese, G., Draetta, G. F., & Chin, L. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.01.019 · Cited by 306
CRISPR/Cas9-mediated efficient targeted mutagenesis in Chardonnay (Vitis vinifera L.)
Ren, C., Liu, X., Zhang, Z., Wang, Y., Duan, W., Li, S., & Liang, Z. (2016) · Scientific Reports · doi:10.1038/srep32289 · Cited by 310
Refined sgRNA efficacy prediction improves large- and small-scale CRISPR–Cas9 applications
Labuhn, M., Adams, F. F., Ng, M. S. W., Knoess, S., Schambach, A., Charpentier, E., Schwarzer, A., Mateo, J. L., Klusmann, J., & Heckl, D. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1268 · Cited by 302
A conformational checkpoint between DNA binding and cleavage by CRISPR-Cas9
Dagdas, Y. S., Chen, J. S., Sternberg, S. H., Doudna, J. A., & Yildiz, A. (2017) · Science Advances · doi:10.1126/sciadv.aao0027 · Cited by 293
CRISPR/Cas9-Mediated Genome Editing of Herpesviruses Limits Productive and Latent Infections
van Diemen, F. R., Kruse, E. M., Hooykaas, M. J. G., Bruggeling, C. E., Schürch, A. C., van Ham, P. M., Imhof, S. M., Nijhuis, M., Wiertz, E. J. H. J., & Lebbink, R. J. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005701 · Cited by 289
A CRISPRi screen in E. coli reveals sequence-specific toxicity of dCas9
Cui, L., Vigouroux, A., Rousset, F., Varet, H., Khanna, V., & Bikard, D. (2018) · Nature Communications · doi:10.1038/s41467-018-04209-5 · Cited by 284
Genome editing in cotton with the CRISPR/cas9 system
Gao, W., Long, L., Tian, X., Xu, F., Liu, J., Singh, P. K., Botella, J. R., & Song, C. (2017) · Frontiers in Plant Science · doi:10.3389/fpls.2017.01364 · Cited by 254
Writing of H3K4Me3 overcomes epigenetic silencing in a sustained but context-dependent manner
Cano-Rodríguez, D., Gjaltema, R. A. F., Jilderda, L. J., Jellema, P. G., Dokter‐Fokkens, J., Ruiters, M. H. J., & Rots, M. G. (2016) · Nature Communications · doi:10.1038/ncomms12284 · Cited by 277
Orthogonal gene knockout and activation with a catalytically active Cas9 nuclease
Dahlman, J. E., Abudayyeh, O. O., Joung, J., Gootenberg, J. S., Zhang, F., & Konermann, S. (2015) · Nature Biotechnology · doi:10.1038/nbt.3390 · Cited by 266
CRISPR/cas systems redefine nucleic acid detection: Principles and methods
Wang, M., Zhang, R., & Li, J. (2020) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2020.112430 · Cited by 273
Streptococcus thermophilus CRISPR-cas9 systems enable specific editing of the human genome
Müller, M., Lee, C. M., Gasiunas, G., Davis, T. H., Cradick, T. J., Siksnys, V., Bao, G., Cathomen, T., & Mussolino, C. (2016) · Molecular Therapy · doi:10.1038/mt.2015.218 · Cited by 254
Real-time observation of DNA recognition and rejection by the RNA-guided endonuclease Cas9
Singh, D., Sternberg, S. H., Fei, J., Doudna, J. A., & Ha, T. (2016) · Nature Communications · doi:10.1038/ncomms12778 · Cited by 269
Quan, J., Langelier, C., Kuchta, A. L., Batson, J., Teyssier, N., Lyden, A., Caldera, S., McGeever, A., Dimitrov, B., King, R., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz418 · Cited by 265
CRISPR/Cas9‐mediated genome engineering: An adeno‐associated viral (AAV) vector toolbox
Senís, E., Fatouros, C., Große, S., Wiedtke, E., Niopek, D., Mueller, A., Börner, K., & Grimm, D. (2014) · Biotechnology Journal · doi:10.1002/biot.201400046 · Cited by 268
CRISPR technologies for genome, epigenome and transcriptome editing
Villiger, L., Joung, J., Koblan, L. W., Weissman, J. S., Abudayyeh, O. O., & Gootenberg, J. S. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00697-6 · Cited by 280
Zhu, X., Xu, Y., Yu, S., Lu, L., Ding, M., Cheng, J., Song, G., Gao, X., Yao, L., Fan, D., et al. (2014) · Scientific Reports · doi:10.1038/srep06420 · Cited by 264
Multi‐input CRISPR/Cas genetic circuits that interface host regulatory networks
Nielsen, A. A. K., & Voigt, C. A. (2014) · Molecular Systems Biology · doi:10.15252/msb.20145735 · Cited by 259
Dramatic Enhancement of Genome Editing by CRISPR/Cas9 Through Improved Guide RNA Design
Farboud, B., & Meyer, B. J. (2015) · Genetics · doi:10.1534/genetics.115.175166 · Cited by 237
The Neisseria meningitidis CRISPR-Cas9 System Enables Specific Genome Editing in Mammalian Cells
Lee, C. M., Cradick, T. J., & Bao, G. (2016) · Molecular Therapy · doi:10.1038/mt.2016.8 · Cited by 250
Review of CRISPR/Cas9 sgRNA Design Tools
Cui, Y., Xu, J., Cheng, M., Liao, X., & Peng, S. (2018) · Interdisciplinary Sciences Computational Life Sciences · doi:10.1007/s12539-018-0298-z · Cited by 253
Multiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM
Wong, A. S. L., Choi, G. C. G., Cui, C. H., Pregernig, G., Milani, P., Adam, M., Perli, S. D., Kazer, S. W., Gaillard, A., Hermann, M., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1517883113 · Cited by 240
Konstantakos, V., Nentidis, A., Krithara, A., & Παλιούρας, Γ. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac192 · Cited by 263
Live cell imaging of low- and non-repetitive chromosome loci using CRISPR-Cas9
Qin, P., Parlak, M., Kuscu, C., Bandaria, J. N., Mir, M., Szlachta, K. A., Singh, R., Darzacq, X., Yıldız, A., & Adli, M. (2017) · Nature Communications · doi:10.1038/ncomms14725 · Cited by 238
Methods and Applications of CRISPR-Mediated Base Editing in Eukaryotic Genomes
Hess, G. T., Tycko, J., Yao, D., & Bassik, M. C. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.09.029 · Cited by 234
Single Cas9 nickase induced generation of NRAMP1 knockin cattle with reduced off-target effects
Gao, Y., Wu, H., Wang, Y., Liu, X., Chen, L., Li, Q., Cui, C., Liu, X., Zhang, J., & Zhang, Y. (2017) · Genome biology · doi:10.1186/s13059-016-1144-4 · Cited by 246
Selection of highly efficient sgRNAs for CRISPR/Cas9-based plant genome editing
Liang, G., Zhang, H., Lou, D., & Yu, D. (2016) · Scientific Reports · doi:10.1038/srep21451 · Cited by 240
The New State of the Art: Cas9 for Gene Activation and Repression
Russa, M. F. L., & Qi, L. S. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00512-15 · Cited by 241
A CRISPR view of developmentPreprint
Harrison, M. M., Jenkins, B., O’Connor-Giles, K. M., & Wildonger, J. (2014) · Genes & Development · doi:10.1101/gad.248252.114 · Cited by 234
Cas9-chromatin binding information enables more accurate CRISPR off-target prediction
Singh, R., Kuscu, C., Quinlan, A., Qi, Y., & Adli, M. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv575 · Cited by 217
A genome-wide analysis of Cas9 binding specificity using ChIP-seq and targeted sequence capture
O'Geen, H., Henry, I. M., Bhakta, M. S., Meckler, J. F., & Segal, D. J. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv137 · Cited by 219
Jensen, K. T., Fløe, L., Petersen, T. S., Huang, J., Xu, F., Bolund, L., Luo, Y., & Lin, L. (2017) · FEBS Letters · doi:10.1002/1873-3468.12707 · Cited by 225
FUT8 promotes breast cancer cell invasiveness by remodeling TGF-β receptor core fucosylation
Tu, C.-F., Wu, M., Lin, Y., Kannagi, R., & Yang, R. (2017) · Breast Cancer Research · doi:10.1186/s13058-017-0904-8 · Cited by 229
Efficient Genome Editing in Clostridium cellulolyticum via CRISPR-Cas9 Nickase
Xu, T., Li, Y., Shi, Z. J., Hemme, C. L., Li, Y., Zhu, Y., Nostrand, J. D. V., He, Z., & Zhou, J. Z. (2015) · Applied and Environmental Microbiology · doi:10.1128/aem.00873-15 · Cited by 231
Lessons from Domestication: Targeting Cis-Regulatory Elements for Crop Improvement
Swinnen, G., Goossens, A., & Pauwels, L. (2016) · Trends in Plant Science · doi:10.1016/j.tplants.2016.01.014 · Cited by 224
RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection
Wang, J., & Quake, S. R. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1410785111 · Cited by 220
CRISPR-Cas9 nuclear dynamics and target recognition in living cells
Ma, H., Tu, L., Naseri, A., Huisman, M., Zhang, S., Grünwald, D., & Pederson, T. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201604115 · Cited by 224
CRISPR/Cas9 advances engineering of microbial cell factories
Jakočiūnas, T., Jensen, M. K., & Keasling, J. D. (2015) · Metabolic Engineering · doi:10.1016/j.ymben.2015.12.003 · Cited by 225
Metadata
- Authors
- Wu, X., Scott, D. A., Kriz, A. J., Chiu, A. C., Hsu, P. D., Dadon, D. B., Cheng, A. W., Trevino, A. E., Konermann, S., Chen, S., Jaenisch, R., Zhang, F., & Sharp, P. A.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- Broad Institute (US)
- Massachusetts Institute of Technology (US)
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Zhang, Feng
- Sharp, Phillip A
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2014-04-20
- Volume
- 32
- Issue
- 7
- Pages
- 670-676
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC4145672
- OpenAlex
- W1506494596
- Cited by
- 944
- References
- 47
- Citations by year
- 2026: 26 · 2025: 42 · 2024: 56 · 2023: 61 · 2022: 73 · 2021: 63 · 2020: 75 · 2019: 80 · 2018: 81 · 2017: 97 · 2016: 123 · 2015: 111 · 2014: 54
- FWCI
- 52.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- eScholarship (California Digital Library) (submittedVersion)
- PMC
- Funders
- Howard Hughes Medical Institute
- National Institute of Mental Health (DP1MH100706)
- National Cancer Institute (R01CA133404, P01CA042063, P30CA014051, P30-CA-14051, P01 CA 42063)
- National Institute of General Medical Sciences (R01GM034277, R01 GM34277, R37GM034277, T32GM007287)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK097768)
- National Center for Chronic Disease Prevention and Health Promotion (1DP1-MH100706)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R37HD045022)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- Cas9, CRISPR/Cas9, dCas9, genome-wide binding sites, single guide RNA, Streptococcus pyogenes, mouse embryonic stem cells, off-target binding, seed sequence, protospacer adjacent motif, chromatin accessibility, DNA cleavage, target specificity
- MeSH terms
- Animals, Base Sequence, Binding Sites, Cells, Cultured, Deoxyribonuclease I, DNA-Binding Proteins, Models, Genetic, Molecular Sequence Data, Protein Binding, Genome, Mice, Embryonic Stem Cells, CRISPR-Cas Systems
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
