Crystal structure of Cas9 in complex with guide RNA and target DNA
Open accessAbstract
The CRISPR-associated endonuclease Cas9 can be targeted to specific genomic loci by single guide RNAs (sgRNAs). Here, we report the crystal structure of Streptococcus pyogenes Cas9 in complex with sgRNA and its target DNA at 2.5 Å resolution. The structure revealed a bilobed architecture composed of target recognition and nuclease lobes, accommodating the sgRNA:DNA heteroduplex in a positively charged groove at their interface. Whereas the recognition lobe is essential for binding sgRNA and DNA, the nuclease lobe contains the HNH and RuvC nuclease domains, which are properly positioned for cleavage of the complementary and noncomplementary strands of the target DNA, respectively. The nuclease lobe also contains a carboxyl-terminal domain responsible for the interaction with the protospacer adjacent motif (PAM). This high-resolution structure and accompanying functional analyses have revealed the molecular mechanism of RNA-guided DNA targeting by Cas9, thus paving the way for the rational design of new, versatile genome-editing technologies.
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SpCas9-NG shows reduced editing efficiency on 5′-NGC-3′ PAM targets and tends to increase off-target activity.
“For example, SpCas9-NG shows reduced editing efficiency on 5′-NGC-3′ PAM targets and tends to increase off-target activity (Nishimasu et al., 2014).”
From Emerging applications of gene editing technologies for the development of climate-resilient crops (2025) · cites this paper as Nishimasu et al., 2014
The Results section on PAM specificity examines SpCas9 and PI-domain chimeras at NGG and NGGNG PAMs, not SpCas9-NG at NGC targets. A search of our copy for SpCas9-NG, NGC editing efficiency, and off-target activity found no passage assessing the claimed effects. (LLM, conf=0.75)
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Sheldrick, G. M. (2007) · Acta Crystallographica Section A Foundations of Crystallography · doi:10.1107/s0108767307043930 · Cited by 87,861 · see citing works
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302 · see citing works
<i>Coot</i> : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571 · see citing works
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 · see citing works
Kabsch, W. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909047337 · Cited by 16,463 · see citing works
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 · see citing works
Self-citationRNA-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 · see citing works
PHENIX: a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkòczi, G., Chen, V. B., Davis, I., Echols, N., Headd, J. J., Hung, L., Kapral, G. J., Grosse‐Kunstleve, R. W., et al. (2012) · International Tables for Crystallography · doi:10.1107/97809553602060000865 · Cited by 7,334 · see citing works
CRISPR Provides Acquired Resistance Against Viruses in Prokaryotes
Barrangou, R., Fremaux, C., Deveau, H., Richards, M., Boyaval, P., Moineau, S., Romero, D. A., & Horvath, P. (2007) · Science · doi:10.1126/science.1138140 · Cited by 6,304 · see citing works
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 · see citing works
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 · see citing works
Cpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System
Zetsche, B., Gootenberg, J. S., Abudayyeh, O. O., Slaymaker, I. M., Makarova, K. S., Essletzbichler, P., Volz, S. E., Joung, J., John van der, O. O. S. T., Regev, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.09.038 · Cited by 4,750 · see citing works
How good are my data and what is the resolution?
Evans, P. R., & Murshudov, G. N. (2013) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444913000061 · Cited by 4,747 · see citing works
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 · see citing works
<i>PHENIX</i> : building new software for automated crystallographic structure determination
Adams, P. D., Grosse-Kunstleve, R. W., Hung, L.-W., Ioerger, T. R., McCoy, A. J., Moriarty, N. W., Read, R. J., Sacchettini, J. C., Sauter, N. K., & Terwilliger, T. C. (2002) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444902016657 · Cited by 4,361 · see citing works
The HHpred interactive server for protein homology detection and structure prediction
Söding, J., Biegert, A., & Lupas, A. N. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki408 · Cited by 3,703 · see citing works
CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes
Gilbert, L. A., Larson, M. H., Morsut, L., Liu, Z., Brar, G. A., Torres, S. E., Stern-Ginossar, N., Brandman, O., Whitehead, E. H., Doudna, J. A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.044 · Cited by 3,696 · see citing works
Dali server: conservation mapping in 3D
Holm, L., & Rosenstr�m, P. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq366 · Cited by 3,640 · see citing works
Wang, H., Yang, H., Shivalila, C. S., Dawlaty, M. M., Cheng, A. W., Zhang, F., & Jaenisch, R. (2013) · Cell · doi:10.1016/j.cell.2013.04.025 · Cited by 3,495 · see citing works
Self-citationDouble nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity
Ran, F. A., Hsu, P. D., Lin, C.-Y., Gootenberg, J. S., Konermann, S., Trevino, A. E., Scott, D. A., Inoue, A., Matoba, S., Zhang, Y., et al. (2013) · Cell · doi:10.1016/j.cell.2013.08.021 · Cited by 3,299 · see citing works
High-Frequency off-Target Mutagenesis Induced by CRISPR-Cas Nucleases in Human Cells
Fu, Y., Foden, J. A., Khayter, C., Maeder, M. L., Reyon, D., Joung, J. K., & Sander, J. D. (2013) · Nature Biotechnology · doi:10.1038/nbt.2623 · Cited by 3,292 · see citing works
Efficient genome editing in zebrafish using a CRISPR-Cas system
Hwang, W. Y., Fu, Y., Reyon, D., Maeder, M. L., Tsai, S. Q., Sander, J. D., Peterson, R. T., Yeh, J.-R. J., & Joung, J. K. (2013) · Nature Biotechnology · doi:10.1038/nbt.2501 · Cited by 2,937 · see citing works
Genetic screens in human cells using the CRISPR-Cas9 system
Wang, T., Wei, J. J., Sabatini, D. M., & Lander, E. S. (2014) · Science · doi:10.1126/science.1246981 · Cited by 2,856 · see citing works
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 · see citing works
Gasiunas, G., Barrangou, R., Horvath, P., & Siksnys, V. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208507109 · Cited by 2,769 · see citing works
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 · see citing works
High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects
Kleinstiver, B. P., Pattanayak, V., Prew, M. S., Tsai, S. Q., Nguyen, N. T., Zheng, Z., & Joung, J. K. (2016) · Nature · doi:10.1038/nature16526 · Cited by 2,673 · see citing works
Small CRISPR RNAs Guide Antiviral Defense in Prokaryotes
Brouns, S. J. J., Jore, M. M., Lundgren, M., Westra, E. R., Slijkhuis, R. J. H., Snijders, A. P., Dickman, M. J., Makarova, K. S., Koonin, E. V., & John van der, O. O. S. T. (2008) · Science · doi:10.1126/science.1159689 · Cited by 2,593 · see citing works
CRISPR RNA Maturation by Trans-Encoded Small RNA and Host Factor RNase III
Deltcheva, E., Chylinski, K., Sharma, C. M., Gonzales, K., Chao, Y., Pirzada, Z. A., Eckert, M. R., Vogel, J., & Charpentier, E. (2011) · Nature · doi:10.1038/nature09886 · Cited by 2,563 · see citing works
An updated evolutionary classification of CRISPR–Cas systems
Makarova, K. S., Wolf, Y. I., Alkhnbashi, O. S., Costa, F., Shah, S. A., Saunders, S. J., Barrangou, R., Brouns, S. J. J., Charpentier, E., Haft, D. H., et al. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3569 · Cited by 2,504 · see citing works
CRISPR/Cas, the Immune System of Bacteria and Archaea
Horvath, P., & Barrangou, R. (2010) · Science · doi:10.1126/science.1179555 · Cited by 2,471 · see citing works
Rationally engineered Cas9 nucleases with improved specificity
Slaymaker, I. M., Gao, L., Zetsche, B., Scott, D. A., Yan, W. X., & Zhang, F. (2016) · Science · doi:10.1126/science.aad5227 · Cited by 2,414 · see citing works
The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA
Garneau, J. E., Dupuis, M.-È., Villion, M., Romero, D. A., Barrangou, R., Boyaval, P., Fremaux, C., Horvath, P., Magadán, A. H., & Moineau, S. (2010) · Nature · doi:10.1038/nature09523 · Cited by 2,336 · see citing works
Fortelle, E. D. L., & Bricogne, G. (1997) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(97)76073-7 · Cited by 1,893 · see citing works
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 1,878 · see citing works
The Buccaneer software for automated model building. 1. Tracing protein chains
Cowtan, K. D. (2006) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444906022116 · Cited by 1,834 · see citing works
DNA interrogation by the CRISPR RNA-guided endonuclease Cas9
Sternberg, S. H., Redding, S., Jínek, M., Greene, E. C., & Doudna, J. A. (2014) · Nature · doi:10.1038/nature13011 · Cited by 1,775 · see citing works
Mali, P., Aach, J., Stranges, P. B., Esvelt, K. M., Moosburner, M., Kosuri, S., Yang, L., & Church, G. M. (2013) · Nature Biotechnology · doi:10.1038/nbt.2675 · Cited by 1,752 · cited 4× · see citing works
“The Type II CRISPR system was the first to be adapted for facilitating genome editing in eukaryotic cells (Cong et al., 2013; Mali et al., 2013b).”
InfluentialCRISPR Interference Limits Horizontal Gene Transfer in Staphylococci by Targeting DNA
Marraffini, L. A., & Sontheimer, E. J. (2008) · Science · doi:10.1126/science.1165771 · Cited by 1,752 · see citing works
Analysis Tool Web Services from the EMBL-EBI
McWilliam, H., Li, W., Uludağ, M., Squizzato, S., Park, Y. M., Buso, N., Cowley, A., & López, R. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt376 · Cited by 1,636 · see citing works
Yang, H., Wang, H., Shivalila, C. S., Cheng, A. W., Shi, L., & Jaenisch, R. (2013) · Cell · doi:10.1016/j.cell.2013.08.022 · Cited by 1,596 · see citing works
Gouet, P. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg556 · Cited by 1,505 · see citing works
Short motif sequences determine the targets of the prokaryotic CRISPR defence system
Mojica, F. J. M., Díez‐Villaseñor, C., García‐Martínez, J., & Almendros, C. (2009) · Microbiology · doi:10.1099/mic.0.023960-0 · Cited by 1,500 · see citing works
Pattanayak, V., Lin, S., Guilinger, J. P., Ma, E., Doudna, J. A., & Liu, D. R. (2013) · Nature Biotechnology · doi:10.1038/nbt.2673 · Cited by 1,487 · cited 2× · see citing works
“This is consistent with previous reports that the 10–12 bp PAM-proximal ‘‘seed’’ region is critical for the Cas9-catalyzed DNA cleavage (Cong et al., 2013; Fu et al., 2013; Hsu et al., 2013; Jinek et al., 2012; Mali et al., 2013a; Pattanayak et al., 2013).”
RNA-guided gene activation by CRISPR-Cas9-based transcription factors
Perez-Pinera, P., Kocak, D. D., Vockley, C. M., Adler, A. F., Kabadi, A. M., Polstein, L. R., Thakore, P. I., Glass, K. A., Ousterout, D. G., Leong, K. W., et al. (2013) · Nature Methods · doi:10.1038/nmeth.2600 · Cited by 1,328 · see citing works
Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease
Anders, C., Niewoehner, O., Duerst, A., & Jínek, M. (2014) · Nature · doi:10.1038/nature13579 · Cited by 1,319 · see citing works
CRISPR RNA–guided activation of endogenous human genes
Maeder, M. L., Linder, S. J., Cascio, V. M., Fu, Y., Ho, Q. H., & Joung, J. K. (2013) · Nature Methods · doi:10.1038/nmeth.2598 · Cited by 1,249 · see citing works
Structures of Cas9 endonucleases reveal RNA-mediated conformational activation
Jinek, M., Jiang, F., Taylor, D. W., Sternberg, S. H., Kaya, E., Ma, E., Anders, C., Hauer, M., Zhou, K., Lin, S., et al. (2014) · Science · doi:10.1126/science.1247997 · Cited by 1,230 · see citing works
Discovery and Functional Characterization of Diverse Class 2 CRISPR-Cas Systems
Shmakov, S., Abudayyeh, O. O., Makarova, K. S., Wolf, Y. I., Gootenberg, J. S., Semenova, E., Станиславович, М. Л., Joung, J., Konermann, S., Severinov, K., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.10.008 · Cited by 1,221 · see citing works
The role of DNA shape in protein–DNA recognition
Rohs, R., West, S. M., Sosinsky, A., Liu, P., Mann, R. S., & Honig, B. (2009) · Nature · doi:10.1038/nature08473 · Cited by 1,096 · see citing works
Golden Gate Shuffling: A One-Pot DNA Shuffling Method Based on Type IIs Restriction Enzymes
Engler, C., Gruetzner, R., Kandzia, R., & Marillonnet, S. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005553 · Cited by 1,028 · see citing works
CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea
Marraffini, L. A., & Sontheimer, E. J. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2749 · Cited by 1,011 · see citing works
Genome Engineering of Drosophila with the CRISPR RNA-Guided Cas9 Nuclease
Gratz, S. J., Cummings, A. M., Nguyen, J. N., Hamm, D. C., Donohue, L. K., Harrison, M. M., Wildonger, J., & O’Connor-Giles, K. M. (2013) · Genetics · doi:10.1534/genetics.113.152710 · Cited by 959 · see citing works
The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli
Sapranauskas, R., Gasiūnas, G., Fremaux, C., Barrangou, R., Horvath, P., & Šikšnys, V. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr606 · Cited by 835 · see citing works
CRISPR-Cas immunity in prokaryotes
Marraffini, L. A. (2015) · Nature · doi:10.1038/nature15386 · Cited by 830 · see citing works
Optical control of mammalian endogenous transcription and epigenetic states
Konermann, S., Brigham, M. D., Trevino, A. E., Hsu, P. D., Heidenreich, M., Cong, L., Platt, R. J., Scott, D. A., Church, G. M., & Zhang, F. (2013) · Nature · doi:10.1038/nature12466 · Cited by 803 · see citing works
Functional annotation of native enhancers with a Cas9–histone demethylase fusion
Kearns, N. A., Pham, H., Tabak, B., Genga, R. M., Silverstein, N. J., Garber, M., & Maehr, R. (2015) · Nature Methods · doi:10.1038/nmeth.3325 · Cited by 656 · see citing works
CRISPR/Cas System and Its Role in Phage-Bacteria Interactions
Deveau, H., Garneau, J. E., & Moineau, S. (2010) · Annual Review of Microbiology · doi:10.1146/annurev.micro.112408.134123 · Cited by 624 · see citing works
Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition
Kleinstiver, B. P., Prew, M. S., Tsai, S. Q., Nguyen, N. T., Topkar, V. V., Zheng, Z., & Joung, J. K. (2015) · Nature Biotechnology · doi:10.1038/nbt.3404 · Cited by 611 · see citing works
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 551 · see citing works
A CRISPR/Cas system mediates bacterial innate immune evasion and virulence
Sampson, T. R., Saroj, S. D., Llewellyn, A. C., Tzeng, Y., & Weiss, D. S. (2013) · Nature · doi:10.1038/nature12048 · Cited by 441 · see citing works
CRISPR-based adaptive immune systems
Terns, M. P., & Terns, R. M. (2011) · Current Opinion in Microbiology · doi:10.1016/j.mib.2011.03.005 · Cited by 440 · see citing works
Crystal Structure of Staphylococcus aureus Cas9
Nishimasu, H., Cong, L., Yan, W. X., Ran, F. A., Zetsche, B., Li, Y., Kurabayashi, A., Ishitani, R., Zhang, F., & Nureki, O. (2015) · Cell · doi:10.1016/j.cell.2015.08.007 · Cited by 430 · see citing works
Structures of the RNA-guided surveillance complex from a bacterial immune system
Wiedenheft, B., Lander, G. C., Zhou, K., Jore, M. M., Brouns, S. J. J., John van der, O. O. S. T., Doudna, J. A., & Nogales, E. (2011) · Nature · doi:10.1038/nature10402 · Cited by 398 · see citing works
Fonfara, I., Rhun, A. L., Chylinski, K., Makarova, K. S., Lécrivain, A.-L., Bzdrenga, J., Koonin, E. V., & Charpentier, E. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1074 · Cited by 329 · see citing works
Atomic structure of the RuvC resolvase: A holliday junction-specific endonuclease from E. coli
Ariyoshi, M., Vassylyev, D. G., Iwasaki, H., Nakamura, H., Shinagawa, H., & Morikawa, K. (1994) · Cell · doi:10.1016/0092-8674(94)90280-1 · Cited by 284 · see citing works
Rapid characterization of CRISPR-Cas9 protospacer adjacent motif sequence elements
Karvelis, T., Gasiūnas, G., Young, J. K., Bigelyte, G., Šilanskas, A., Cigan, M., & Šikšnys, V. (2015) · Genome biology · doi:10.1186/s13059-015-0818-7 · Cited by 222 · see citing works
Westra, E. R., Semenova, E., Datsenko, K. A., Jackson, R. N., Wiedenheft, B., Severinov, K., & Brouns, S. J. J. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003742 · Cited by 216 · see citing works
Surveillance and Processing of Foreign DNA by the Escherichia coli CRISPR-Cas System
Redding, S., Sternberg, S. H., Marshall, M., Gibb, B., Bhat, P., Guegler, C. K., Wiedenheft, B., Doudna, J. A., & Greene, E. C. (2015) · Cell · doi:10.1016/j.cell.2015.10.003 · Cited by 187 · see citing works
Structure of an RNA Silencing Complex of the CRISPR-Cas Immune System
Spilman, M. S., Cocozaki, A. I., Hale, C. R., Shao, Y., Ramia, N. F., Terns, R., Terns, M. P., Li, H., & Stagg, S. M. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.09.008 · Cited by 130 · see citing works
Crystal structure of T4 endonuclease VII resolving a Holliday junction
Biertümpfel, C., Yang, W., & Suck, D. (2007) · Nature · doi:10.1038/nature06152 · Cited by 125 · see citing works
DNA binding and cleavage by the periplasmic nuclease Vvn: a novel structure with a known active site
Li, C., Hor, L., Chang, Z.-F., Tsai, L., Yang, W., & Yuan, H. S. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg377 · Cited by 114 · see citing works
Crystal structure of RuvC resolvase in complex with Holliday junction substrate
Górecka, K. M., Komorowska, W., & Nowotny, M. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt769 · Cited by 70 · see citing works
Chen, L., Shi, K., Yin, Z., & Aihara, H. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1015 · Cited by 32 · see citing works
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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 · see citing works
Search-and-replace genome editing without double-strand breaks or donor DNA
Anzalone, A. V., Randolph, P. B., Davis, J. R., Sousa, A. A., Koblan, L. W., Levy, J. M., Chen, P. J., Wilson, C., Newby, G. A., Raguram, A., et al. (2019) · Nature · doi:10.1038/s41586-019-1711-4 · Cited by 4,767 · see citing works
Cpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System
Zetsche, B., Gootenberg, J. S., Abudayyeh, O. O., Slaymaker, I. M., Makarova, K. S., Essletzbichler, P., Volz, S. E., Joung, J., John van der, O. O. S. T., Regev, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.09.038 · Cited by 4,750 · see citing works
CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity
Chen, J. S., Ma, E., Harrington, L. B., Da Costa, M., Tian, X., Palefsky, J. M., & Doudna, J. A. (2018) · Science · doi:10.1126/science.aar6245 · Cited by 4,507 · see citing works
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 · see citing works
High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects
Kleinstiver, B. P., Pattanayak, V., Prew, M. S., Tsai, S. Q., Nguyen, N. T., Zheng, Z., & Joung, J. K. (2016) · Nature · doi:10.1038/nature16526 · Cited by 2,673 · see citing works
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 · see citing works
Self-citationRationally engineered Cas9 nucleases with improved specificity
Slaymaker, I. M., Gao, L., Zetsche, B., Scott, D. A., Yan, W. X., & Zhang, F. (2016) · Science · doi:10.1126/science.aad5227 · Cited by 2,414 · see citing works
Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors
Anzalone, A. V., Koblan, L. W., & Liu, D. R. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0561-9 · Cited by 2,237 · see citing works
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 · see citing works
A CRISPR/Cas9 toolkit for multiplex genome editing in plants
Xing, H.-L., Dong, L., Wang, Z.-P., Zhang, H.-Y., Han, C.-Y., Liu, B., Wang, X.-C., & Chen, Q.-J. (2014) · BMC Plant Biology · doi:10.1186/s12870-014-0327-y · Cited by 1,684 · see citing works
Base editing: precision chemistry on the genome and transcriptome of living cells
Rees, H. A., & Liu, D. R. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0059-1 · Cited by 1,675 · see citing works
The CRISPR tool kit for genome editing and beyond
Adli, M. (2018) · Nature Communications · doi:10.1038/s41467-018-04252-2 · Cited by 1,642 · see citing works
CRISPR-Cas12a-assisted nucleic acid detection
Li, S., Cheng, Q., Wang, J.-M., Li, X., Zhang, Z., Cao, R., Cao, R.-B., Zhao, G.-P., & Wang, J. (2018) · Cell Discovery · doi:10.1038/s41421-018-0028-z · Cited by 1,542 · see citing works
Diversity, classification and evolution of CRISPR-Cas systems
Koonin, E. V., Makarova, K. S., & Zhang, F. (2017) · Current Opinion in Microbiology · doi:10.1016/j.mib.2017.05.008 · Cited by 1,423 · see citing works
Self-citationOff-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 · see citing works
Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease
Anders, C., Niewoehner, O., Duerst, A., & Jínek, M. (2014) · Nature · doi:10.1038/nature13579 · Cited by 1,319 · see citing works
Enhanced proofreading governs CRISPR-Cas9 targeting accuracy
Chen, J. S., Dagdas, Y. S., Kleinstiver, B. P., Welch, M. M., Sousa, A. A., Harrington, L. B., Sternberg, S. H., Joung, J. K., Yildiz, A., & Doudna, J. A. (2017) · Nature · doi:10.1038/nature24268 · Cited by 1,168 · see citing works
Discovery and Functional Characterization of Diverse Class 2 CRISPR-Cas Systems
Shmakov, S., Abudayyeh, O. O., Makarova, K. S., Wolf, Y. I., Gootenberg, J. S., Semenova, E., Станиславович, М. Л., Joung, J., Konermann, S., Severinov, K., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.10.008 · Cited by 1,221 · see citing works
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 · see citing works
Self-citationAdamson, B., Norman, T. M., Jost, M., Cho, M. Y., Nuñez, J. K., Chen, Y., Villalta, J. E., Gilbert, L. A., Horlbeck, M. A., Hein, M. Y., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.048 · Cited by 1,215 · see citing works
Richardson, C. D., Ray, G. J., DeWitt, M. A., Curie, G. L., & Corn, J. E. (2016) · Nature Biotechnology · doi:10.1038/nbt.3481 · Cited by 1,098 · see citing works
A guide to genome engineering with programmable nucleases
Kim, S., & Kim, J. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3686 · Cited by 1,162 · see citing works
CRISPR/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 1,165 · see citing works
CRISPR-Cas12a has both cis- and trans-cleavage activities on single-stranded DNA
Li, S., Cheng, Q., Liu, J.-K., Nie, X., Zhao, G., & Wang, J. (2018) · Cell Research · doi:10.1038/s41422-018-0022-x · Cited by 1,140 · see citing works
Diversity and evolution of class 2 CRISPR–Cas systems
Shmakov, S., Smargon, A. A., Scott, D. A., Cox, D. B. T., Pyzocha, N., Yan, W. X., Abudayyeh, O. O., Gootenberg, J. S., Makarova, K. S., Wolf, Y. I., et al. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.184 · Cited by 1,056 · see citing works
The Biology of CRISPR-Cas: Backward and Forward
Hille, F., Richter, H., Wong, S. P., Bratovič, M., Ressel, S., & Charpentier, E. (2018) · Cell · doi:10.1016/j.cell.2017.11.032 · Cited by 1,019 · see citing works
Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells
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., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.2889 · Cited by 944 · see citing works
Biology and Applications of CRISPR Systems: Harnessing Nature’s Toolbox for Genome Engineering
Wright, A. V., Nuñez, J. K., & Doudna, J. A. (2016) · Cell · doi:10.1016/j.cell.2015.12.035 · Cited by 1,001 · see citing works
Multiplex gene editing by CRISPR–Cpf1 using a single crRNA array
Zetsche, B., Heidenreich, M., Mohanraju, P., Fedorova, I., Kneppers, J., DeGennaro, E. M., Winblad, N., Choudhury, S. R., Abudayyeh, O. O., Gootenberg, J. S., et al. (2017) · Nature Biotechnology · doi:10.1038/nbt.3737 · Cited by 926 · see citing works
The CRISPR-associated DNA-cleaving enzyme Cpf1 also processes precursor CRISPR RNA
Fonfara, I., Richter, H., Bratovič, M., Rhun, A. L., & Charpentier, E. (2016) · Nature · doi:10.1038/nature17945 · Cited by 976 · see citing works
Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing
Tsai, S. Q., Wyvekens, N., Khayter, C., Foden, J. A., Thapar, V., Reyon, D., Goodwin, M. J., Aryee, M. J., & Joung, J. K. (2014) · Nature Biotechnology · doi:10.1038/nbt.2908 · Cited by 952 · see citing works
Applications of CRISPR technologies in research and beyond
Barrangou, R., & Doudna, J. A. (2016) · Nature Biotechnology · doi:10.1038/nbt.3659 · Cited by 1,005 · see citing works
Principles of genetic circuit design
Brophy, J. A. N., & Voigt, C. A. (2014) · Nature Methods · doi:10.1038/nmeth.2926 · Cited by 934 · see citing works
Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds
Zalatan, J. G., Lee, M. E., Almeida, R., Gilbert, L. A., Whitehead, E. H., La Russa, M., Tsai, J. C., Weissman, J. S., Dueber, J. E., Qi, L. S., et al. (2015) · Cell · doi:10.1016/j.cell.2014.11.052 · Cited by 938 · see citing works
CRISPR-Cas Systems: Prokaryotes Upgrade to Adaptive Immunity
Barrangou, R., & Marraffini, L. A. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.011 · Cited by 907 · see citing works
Concerning RNA-guided gene drives for the alteration of wild populations
Esvelt, K. M., Smidler, A. L., Catteruccia, F., & Church, G. M. (2014) · eLife · doi:10.7554/elife.03401 · Cited by 857 · see citing works
Guilinger, J. P., Thompson, D. B., & Liu, D. R. (2014) · Nature Biotechnology · doi:10.1038/nbt.2909 · Cited by 836 · see citing works
CRISPR-P 2.0: An Improved CRISPR-Cas9 Tool for Genome Editing in Plants
Liu, H., Ding, Y., Zhou, Y., Jin, W., Xie, K., & Chen, L. (2017) · Molecular Plant · doi:10.1016/j.molp.2017.01.003 · Cited by 843 · see citing works
CRISPR-Cas immunity in prokaryotes
Marraffini, L. A. (2015) · Nature · doi:10.1038/nature15386 · Cited by 830 · see citing works
Repurposing the CRISPR-Cas9 system for targeted DNA methylation
Vojta, A., Dobrinić, P., Tadić, V., Bočkor, L., Korać, P., Jülg, B. D., Klasić, M., & Zoldoš, V. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw159 · Cited by 772 · see citing works
Crystal Structure of Cpf1 in Complex with Guide RNA and Target DNA
Yamano, T., Nishimasu, H., Zetsche, B., Hirano, H., Slaymaker, I. M., Li, Y., Fedorova, I., Nakane, T., Makarova, K. S., Koonin, E. V., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.003 · Cited by 756 · see citing works
Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts
Stewart, M. P., Langer, R., & Jensen, K. F. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00678 · Cited by 748 · see citing works
CRISPR/Cas9 therapeutics: progress and prospects
Li, T., Yang, Y., Qi, H., Cui, W., Zhang, L., Fu, X., He, X., Liu, M., Li, P., & Yu, T. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01309-7 · Cited by 770 · see citing works
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 722 · see citing works
Unravelling the structural and mechanistic basis of CRISPR–Cas systems
John van der, O. O. S. T., Westra, E. R., Jackson, R. N., & Wiedenheft, B. (2014) · Nature Reviews Microbiology · doi:10.1038/nrmicro3279 · Cited by 715 · see citing works
A split-Cas9 architecture for inducible genome editing and transcription modulation
Zetsche, B., Volz, S. E., & Zhang, F. (2015) · Nature Biotechnology · doi:10.1038/nbt.3149 · Cited by 704 · see citing works
Kleinstiver, B. P., Sousa, A. A., Walton, R. T., Tak, Y. E., Hsu, J. Y., Clement, K., Welch, M. M., Horng, J. E., Malagon-Lopez, J., Scarfò, I., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-018-0011-0 · Cited by 680 · see citing works
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 · see citing works
Diverse evolutionary roots and mechanistic variations of the CRISPR-Cas systems
Mohanraju, P., Makarova, K. S., Zetsche, B., Zhang, F., Koonin, E. V., & John van der, O. O. S. T. (2016) · Science · doi:10.1126/science.aad5147 · Cited by 668 · see citing works
A Multifunctional AAV-CRISPR-Cas9 and Its Host Response
Chew, W. L., Tabebordbar, M., Cheng, J. K. W., Mali, P., Wu, E. Y., Ng, A. H. M., Zhu, K., Wagers, A. J., & Church, G. M. (2016) · Nature Methods · doi:10.1038/nmeth.3993 · Cited by 617 · see citing works
Programmable RNA recognition and cleavage by CRISPR/Cas9
O’Connell, M. R., Oakes, B. L., Sternberg, S. H., East-Seletsky, A., Kaplan, M., & Doudna, J. A. (2014) · Nature · doi:10.1038/nature13769 · Cited by 631 · see citing works
Structures of a CRISPR-Cas9 R-loop complex primed for DNA cleavage
Jiang, F., Taylor, D. W., Chen, J. S., Kornfeld, J. E., Zhou, K., Thompson, A. J., Nogales, E., & Doudna, J. A. (2016) · Science · doi:10.1126/science.aad8282 · Cited by 616 · see citing works
Photoactivatable CRISPR-Cas9 for optogenetic genome editing
Nihongaki, Y., Kawano, F., Nakajima, T., & Sato, M. (2015) · Nature Biotechnology · doi:10.1038/nbt.3245 · Cited by 609 · see citing works
Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition
Kleinstiver, B. P., Prew, M. S., Tsai, S. Q., Nguyen, N. T., Topkar, V. V., Zheng, Z., & Joung, J. K. (2015) · Nature Biotechnology · doi:10.1038/nbt.3404 · Cited by 611 · see citing works
Structural Basis for Guide RNA Processing and Seed-Dependent DNA Targeting by CRISPR-Cas12a
Swarts, D. C., John van der, O. O. S. T., & Jínek, M. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.03.016 · Cited by 615 · see citing works
Mechanistic Insights into the cis- and trans-Acting DNase Activities of Cas12a
Swarts, D. C., & Jínek, M. (2019) · Molecular Cell · doi:10.1016/j.molcel.2018.11.021 · Cited by 609 · see citing works
New CRISPR–Cas systems from uncultivated microbes
Burstein, D. E., Harrington, L. B., Strutt, S. C., Probst, A. J., Anantharaman, K., Thomas, B. C., Doudna, J. A., & Banfield, J. F. (2016) · Nature · doi:10.1038/nature21059 · Cited by 574 · see citing works
Hurtado, S., Milem, J. F., Clayton-Pedersen, A. R., & Allen, W. R. (1999) · Cited by 568 · see citing works
The CRISPR-Cas immune system: Biology, mechanisms and applications
Rath, D., Amlinger, L., Rath, A., & Lundgren, M. (2015) · Biochimie · doi:10.1016/j.biochi.2015.03.025 · Cited by 565 · see citing works
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 551 · see citing works
Genome Engineering with Targetable Nucleases
Carroll, D. (2014) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060713-035418 · Cited by 541 · see citing works
CRISPR/Cas system: recent advances and future prospects for genome editing
Manghwar, H., Lindsey, K., Zhang, X., & Jin, S. (2019) · Trends in Plant Science · doi:10.1016/j.tplants.2019.09.006 · Cited by 529 · see citing works
Ishino, Y., Krupovìč, M., & Forterre, P. (2018) · Journal of Bacteriology · doi:10.1128/jb.00580-17 · Cited by 558 · see citing works
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 541 · see citing works
Skourti-Stathaki, K., & Proudfoot, N. J. (2014) · Genes & Development · doi:10.1101/gad.242990.114 · Cited by 521 · see citing works
Directed evolution of CRISPR-Cas9 to increase its specificity
Lee, J. K., Jeong, E., Lee, J., Jung, M., Shin, E., Kim, Y.-H., Lee, K., Jung, I., Kim, D., Kim, S., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05477-x · Cited by 525 · see citing works
The Molecular Architecture for RNA-Guided RNA Cleavage by Cas13a
Liu, L., Li, X., Ma, J., Li, Z., You, L., Wang, J., Wang, M., Zhang, X., & Wang, Y. (2017) · Cell · doi:10.1016/j.cell.2017.06.050 · Cited by 506 · see citing works
Functionally diverse type V CRISPR-Cas systems
Yan, W. X., Hunnewell, P., Alfonse, L. E., Carte, J. M., Keston-Smith, E., Sothiselvam, S., Garrity, A. J., Chong, S., Makarova, K. S., Koonin, E. V., et al. (2018) · Science · doi:10.1126/science.aav7271 · Cited by 509 · see citing works
Origins and evolution of CRISPR-Cas systems
Koonin, E. V., & Makarova, K. S. (2019) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2018.0087 · Cited by 494 · see citing works
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 508 · see citing works
Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing
Yin, H., Song, C.-Q., Suresh, S., Wu, Q., Walsh, S., Rhym, L. H., Mintzer, E., Bolukbasi, M. F., Zhu, L. J., Kauffman, K., et al. (2017) · Nature Biotechnology · doi:10.1038/nbt.4005 · Cited by 499 · see citing works
Classification and evolution of type II CRISPR-Cas systems
Chylinski, K., Makarova, K. S., Charpentier, E., & Koonin, E. V. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku241 · Cited by 498 · see citing works
Mapping the genomic landscape of CRISPR-Cas9 cleavage
Cameron, P., Fuller, C. K., Donohoue, P. D., Jones, B. N., Thompson, M. S., Carter, M. M., Gradia, S., Vidal, B., Garner, E., Slorach, E. M., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4284 · Cited by 443 · see citing works
CRISPR/Cas9 Platforms for Genome Editing in Plants: Developments and Applications
Ma, X., Zhu, Q., Chen, Y., & Liu, Y. (2016) · Molecular Plant · doi:10.1016/j.molp.2016.04.009 · Cited by 480 · see citing works
Base editing: advances and therapeutic opportunities
Porto, E. M., Komor, A. C., Slaymaker, I. M., & Yeo, G. W.-M. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0084-6 · Cited by 475 · see citing works
Direct observation of R-loop formation by single RNA-guided Cas9 and Cascade effector complexes
Szczelkun, M. D., Tikhomirova, M. S., Šinkūnas, T., Gasiūnas, G., Karvelis, T., Pschera, P., Šikšnys, V., & Seidel, R. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402597111 · Cited by 445 · see citing works
Mechanism and Applications of CRISPR/Cas-9-Mediated Genome Editing
Mengstie, M. A., & Wondimu, B. Z. (2021) · Biologics · doi:10.2147/btt.s326422 · Cited by 478 · see citing works
Annotation and Classification of CRISPR-Cas Systems
Makarova, K. S., & Koonin, E. V. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2687-9_4 · Cited by 441 · see citing works
Nguyễn, L. T., Smith, B. M., & Jain, P. (2020) · Nature Communications · doi:10.1038/s41467-020-18615-1 · Cited by 439 · see citing works
Current applications and future perspective of CRISPR/Cas9 gene editing in cancer
Wang, S.-W., Gao, C., Zheng, Y.-M., Yi, L., Lu, J.-C., Huang, X.-Y., Cai, J.-B., Zhang, P.-F., Cui, Y.-H., & Ke, A.-W. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01518-8 · Cited by 478 · see citing works
Crystal Structure of Staphylococcus aureus Cas9
Nishimasu, H., Cong, L., Yan, W. X., Ran, F. A., Zetsche, B., Li, Y., Kurabayashi, A., Ishitani, R., Zhang, F., & Nureki, O. (2015) · Cell · doi:10.1016/j.cell.2015.08.007 · Cited by 430 · see citing works
CRISPR-Cas9 Based Engineering of Actinomycetal Genomes
Tong, Y., Charusanti, P., Zhang, L., Weber, T., & Lee, S. Y. (2015) · ACS Synthetic Biology · doi:10.1021/acssynbio.5b00038 · Cited by 431 · see citing works
CRISPR-Cas12a: Functional overview and applications
Paul, B., & Montoya, G. (2020) · Biomedical Journal · doi:10.1016/j.bj.2019.10.005 · Cited by 437 · see citing works
Engineered Cpf1 variants with altered PAM specificities
Gao, L., Cox, D. B. T., Yan, W. X., Manteiga, J. C., Schneider, M. W., Yamano, T., Nishimasu, H., Nureki, O., Crosetto, N., & Zhang, F. (2017) · Nature Biotechnology · doi:10.1038/nbt.3900 · Cited by 460 · see citing works
Base editing with a Cpf1–cytidine deaminase fusion
Li, X., Wang, Y., Liu, Y., Yang, B., Wang, X., Wei, J., Lu, Z., Zhang, Y., Wu, J., Huang, X., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4102 · Cited by 426 · see citing works
Treatment of a metabolic liver disease by in vivo genome base editing in adult mice
Villiger, L., Grisch‐Chan, H. M., Lindsay, H. A., Ringnalda, F. C. A. S., Pogliano, C. B., Allegri, G., Fingerhut, R., Häberle, J., Matos, J., Robinson, M. D., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0209-1 · Cited by 426 · see citing works
The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases
Altae-Tran, H., Kannan, S., Demircioglu, F. E., Oshiro, R., Nety, S. P., McKay, L. J., Dlakić, M., Inskeep, W. P., Makarova, K. S., Macrae, R. K., et al. (2021) · Science · doi:10.1126/science.abj6856 · Cited by 407 · see citing works
CasX enzymes comprise a distinct family of RNA-guided genome editors
Liu, J.-J., Orlova, N., Oakes, B. L., Ma, E., Spinner, H. B., Baney, K. L. M., Chuck, J., Tan, D., Knott, G. J., Harrington, L. B., et al. (2019) · Nature · doi:10.1038/s41586-019-0908-x · Cited by 446 · see citing works
The crystal structure of Cpf1 in complex with CRISPR RNA
Dong, D., Ren, K., Qiu, X., Zheng, J., Guo, M., Guan, X., Liu, H., Li, N., Zhang, B., Yang, D.-J., et al. (2016) · Nature · doi:10.1038/nature17944 · Cited by 413 · see citing works
Genome-Editing Technologies: Principles and ApplicationsPreprint
Gaj, T., Sirk, S. J., Shui, S., & Liu, J. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a023754 · Cited by 425 · see citing works
Point-of-care CRISPR/Cas nucleic acid detection: Recent advances, challenges and opportunities
van Dongen, J. E., Berendsen, J. T. W., Steenbergen, R. D. M., Wolthuis, R. M. F., Eijkel, J. C. T., & Segerink, L. I. (2020) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2020.112445 · Cited by 420 · see citing works
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 398 · see citing works
A Rapid Method for Directed Gene Knockout for Screening in G0 Zebrafish
Wu, R. S., Lam, I. I., Clay, H., Duong, D. N., Deo, R. C., & Coughlin, S. R. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.06.003 · Cited by 399 · see citing works
The emerging and uncultivated potential of CRISPR technology in plant science
Zhang, Y., Malzahn, A. A., Sretenovic, S., & Qi, Y. (2019) · Nature Plants · doi:10.1038/s41477-019-0461-5 · Cited by 404 · see citing works
CRISPR-Cpf1 assisted genome editing of Corynebacterium glutamicum
Jiang, Y., Qian, F., Yang, J., Liu, Y., Dong, F., Xu, C., Sun, B., Chen, B., Xu, X., Li, Y., et al. (2017) · Nature Communications · doi:10.1038/ncomms15179 · Cited by 391 · see citing works
Deep learning improves prediction of CRISPR–Cpf1 guide RNA activity
Kim, H. K., Min, S., Song, M., Jung, S., Choi, J. W., Kim, Y., Lee, S., Yoon, S., & Kim, S. (2018) · Nature Biotechnology · doi:10.1038/nbt.4061 · Cited by 384 · see citing works
In vivo high-throughput profiling of CRISPR-Cpf1 activity
Kim, H. K., Song, M., Lee, J., Menon, A. V., Jung, S., Kang, Y.-M., Choi, J. W., Woo, E., Koh, H. C., Nam, J.-W., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4104 · Cited by 383 · see citing works
Multiplex CRISPR/Cas9-based genome engineering from a single lentiviral vector
Kabadi, A. M., Ousterout, D. G., Hilton, I. B., & Gersbach, C. A. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku749 · Cited by 371 · see citing works
- Authors
- Nishimasu, H., Ran, F. A., Hsu, P. D., Konermann, S., Shehata, S. I., Dohmae, N., Ishitani, R., Zhang, F., & Nureki, O.
- Affiliations
- Japan Science and Technology Agency (JP)
- Broad Institute (US)
- RIKEN (JP)
- The University of Tokyo (JP)
- Corresponding author
- Zhang, Feng
- Nureki, Osamu
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 156
- Issue
- 5
- Pages
- 935-949
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4139937
- OpenAlex
- W2107959600
- Cited by
- 2,306
- References
- 77
- Citations by year
- 2026: 130 · 2025: 193 · 2024: 221 · 2023: 177 · 2022: 229 · 2021: 218 · 2020: 215 · 2019: 212 · 2018: 191 · 2017: 193 · 2016: 149 · 2015: 93 · 2014: 80 · 2013: 2
- FWCI
- 70.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- PMC
- Funders
- PRESTO from the Japan Science and Technology (JST) Agency
- Drug Discovery and Informatics
- Japan Society for the Promotion of Science (JSPS)
- Core Research for Evolutional Science and Technology (CREST)
- Japan Science and Technology Agency (JST)
- NIH (5DP1-MH100706)
- Keck
- McKnight
- Poitras
- Merkin
- Vallee
- Damon Runyon
- Searle Scholars
- Klingenstein
- Simons Foundations
- Bob Metcalfe
- Jane Pauley
- 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
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- CRISPR/Cas12a, guide RNA, target DNA, RNA-guided DNA cleavage, protospacer adjacent motif, genome editing, crystal structure
- MeSH terms
- Amino Acid Sequence, Bacteria, DNA, Bacterial, Endonucleases, Models, Molecular, Molecular Sequence Data, RNA, Bacterial, Streptococcus pyogenes, Sequence Alignment, Protein Structure, Tertiary, Crystallography, X-Ray, RNA, Small Untranslated, CRISPR-Associated Proteins
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 ›
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