The DOI matches its Crossref record; 130 of the 130 references it cites were found in a registry or an index.
High-throughput functional genomics using CRISPR-Cas9
Open accessAbstract
Forward genetic screens are powerful tools for the discovery and functional annotation of genetic elements. Recently, the RNA-guided CRISPR (clustered regularly interspaced short palindromic repeat)-associated Cas9 nuclease has been combined with genome-scale guide RNA libraries for unbiased, phenotypic screening. In this Review, we describe recent advances using Cas9 for genome-scale screens, including knockout approaches that inactivate genomic loci and strategies that modulate transcriptional activity. We discuss practical aspects of screen design, provide comparisons with RNA interference (RNAi) screening, and outline future applications and challenges.
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
“the deficiencies of RNAi-based methods in the areas of reagent fidelity and scalability make it difficult to use this approach to accurately map drug target interactions across a large matrix of cell lines and drug treatments”
From A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution (2017) · cites this paper as Shalem et al., 2015
Experimental — accuracy not yet measuredIn the citing paper
“This has limited pooled screens largely to vetting genes for their potential impact on cell fitness”
From Protein Barcodes Enable High-Dimensional Single-Cell CRISPR Screens (2018) · cites this paper as Shalem et al., 2015
In the citing paper
“So far three distinct bacterial CRISPR systems have been identified; Type I, II and III, and it is the Type II system that has mainly been adapted for use in artificial gene regulation and genome editing (Kim and Kim 2014; Shalem, Sanjana and Zhang 2015).”
From Candida glabrata : new tools and technologies—expanding the toolkit (2015) · cites this paper as Shalem, Sanjana and Zhang 2015
In the citing paper
“The most commonly used CRISPR Type II system consists of a gRNA and an endonuclease, the CRISPR-associated (Cas) nuclease, Cas9, which cleaves the targeted chromosomal DNA in a site-specific manner triggering endogenous DNA repair systems resulting in genome modification (for an in-depth review, see Doudna and Charpentier 2014; Kim and Kim 2014; Shalem, Sanjana and Zhang 2015).”
From Candida glabrata : new tools and technologies—expanding the toolkit (2015) · cites this paper as Shalem, Sanjana and Zhang 2015
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
Bartel (2004) · doi:10.1016/s0092-8674(04)00045-5 · Cited by 34,714
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
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., & Mello, C. C. (1998) · Nature · doi:10.1038/35888 · Cited by 15,429
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-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
MicroRNAs: small RNAs with a big role in gene regulation
He, L., & Hannon, G. J. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1379 · Cited by 7,118
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
Self-citationImproved vectors and genome-wide libraries for CRISPR screening
Sanjana, N. E., Shalem, O., & Zhang, F. (2014) · Nature Methods · doi:10.1038/nmeth.3047 · Cited by 5,239
Self-citationGenome-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
Self-citationMutations affecting segment number and polarity in Drosophila
Nüsslein‐Volhard, C., & Wieschaus, E. F. (1980) · Nature · doi:10.1038/287795a0 · Cited by 4,370
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
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
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
Self-citationHigh-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
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
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
Self-citationGasiunas, G., Barrangou, R., Horvath, P., & Siksnys, V. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208507109 · Cited by 2,769
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-citationMechanisms of gene silencing by double-stranded RNA
Meister, G., & Tuschl, T. (2004) · Nature · doi:10.1038/nature02873 · Cited by 2,598
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
The ENCODE (ENCyclopedia Of DNA Elements) Project
(2004) · Science · doi:10.1126/science.1105136 · Cited by 2,390
Expression profiling reveals off-target gene regulation by RNAi
Jackson, A. L., Bartz, S. R., Schelter, J., Kobayashi, S. V., Burchard, J., Mao, M., Li, B., Cavet, G., & Linsley, P. S. (2003) · Nature Biotechnology · doi:10.1038/nbt831 · Cited by 2,370
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
Crystal structure of Cas9 in complex with guide RNA and target DNA
Nishimasu, H., Ran, F. A., Hsu, P. D., Konermann, S., Shehata, S. I., Dohmae, N., Ishitani, R., Zhang, F., & Nureki, O. (2014) · Cell · doi:10.1016/j.cell.2014.02.001 · Cited by 2,306
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 Knockin Mice for Genome Editing and Cancer Modeling
Platt, R. J., Chen, S., Zhou, Y., Yim, M. J., Swiech, L., Kempton, H. R., Dahlman, J. E., Parnas, O., Eisenhaure, T. M., Jovanovic, M., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.014 · Cited by 2,001
Self-citationImproving CRISPR-Cas nuclease specificity using truncated guide RNAs
Fu, Y., Sander, J. D., Reyon, D., Cascio, V. M., & Joung, J. K. (2014) · Nature Biotechnology · doi:10.1038/nbt.2808 · Cited by 1,993
Dynamic Imaging of Genomic Loci in Living Human Cells by an Optimized CRISPR/Cas System
Chen, B., Gilbert, L. A., Cimini, B. A., Schnitzbauer, J., Zhang, W., Li, G., Park, J. S., Blackburn, E. H., Weissman, J. S., Qi, L. S., et al. (2013) · Cell · doi:10.1016/j.cell.2013.12.001 · Cited by 1,988
DNA interrogation by the CRISPR RNA-guided endonuclease Cas9
Sternberg, S. H., Redding, S., Jinek, M., Greene, E. C., & Doudna, J. A. (2014) · Nature · doi:10.1038/nature13011 · Cited by 1,822
A Lentiviral RNAi Library for Human and Mouse Genes Applied to an Arrayed Viral High-Content Screen
Moffat, J., Grueneberg, D. A., Yang, X., Kim, S. Y., Kloepfer, A. M., Hinkle, G., Piqani, B., Eisenhaure, T., Luo, B., Grenier, J. K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.01.040 · Cited by 1,804
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
Haffter, P., Granato, M., Brand, M., Mullins, M. C., Hammerschmidt, M., Kane, D. A., Odenthal, J., van Eeden, F. J. M., Jiang, Y., Heisenberg, C., et al. (1996) · Development · doi:10.1242/dev.123.1.1 · Cited by 1,691
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
A Protein-Tagging System for Signal Amplification in Gene Expression and Fluorescence Imaging
Tanenbaum, M. E., Gilbert, L. A., Qi, L. S., Weissman, J. S., & Vale, R. D. (2014) · Cell · doi:10.1016/j.cell.2014.09.039 · Cited by 1,611
Bolotin, A., Quinquis, B., Sorokin, A., & Ehrlich, S. D. (2005) · Microbiology · doi:10.1099/mic.0.28048-0 · Cited by 1,558
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
Gene silencing in mammals by small interfering RNAs
McManus, M. T., & Sharp, P. A. (2002) · Nature Reviews Genetics · doi:10.1038/nrg908 · Cited by 1,400
A genetic screen for mutations affecting embryogenesis in zebrafish
Driever, W., Solnica‐Krezel, L., Schier, A. F., Neuhauss, S. C. F., Malicki, J. J., Stemple, D. L., Stainier, D. Y. R., Zwartkruis, F. J. T., Abdelilah, S., Rangini, Z., et al. (1996) · Development · doi:10.1242/dev.123.1.37 · Cited by 1,338
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
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
CRISPR interference (CRISPRi) for sequence-specific control of gene expression
Larson, M. H., Gilbert, L. A., Wang, X., Lim, W. A., Weissman, J. S., & Qi, L. S. (2013) · Nature Protocols · doi:10.1038/nprot.2013.132 · Cited by 1,241
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
A guide to genome engineering with programmable nucleases
Kim, S., & Kim, J. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3686 · Cited by 1,216
Bikard, D., Jiang, W., Samai, P., Hochschild, A., Zhang, F., & Marraffini, L. A. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt520 · Cited by 1,145
Self-citationJackson, A. L., & Linsley, P. S. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd3010 · Cited by 1,126
A large-scale RNAi screen in human cells identifies new components of the p53 pathway
Berns, K., Hijmans, E. M., Mullenders, J., Brummelkamp, T. R., Velds, A., Heimerikx, M., Kerkhoven, R. M., Madiredjo, M., Nijkamp, W., Weigelt, B., et al. (2004) · Nature Cell Biology · doi:10.1038/nature02371 · Cited by 1,080
Koike-Yusa, H., Li, Y., Tan, E.-P., Velasco-Herrera, M. D. C., & Yusa, K. (2014) · Nature Biotechnology · doi:10.1038/nbt.2800 · Cited by 1,064
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
Self-citationEngineering 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
3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets
Birmingham, A., Anderson, E. M., Reynolds, A., Ilsley-Tyree, D., Leake, D., Fedorov, Y., Baskerville, S., Maksimova, E., Robinson, K., Karpilow, J., et al. (2006) · Nature Methods · doi:10.1038/nmeth854 · Cited by 920
siRNAs: applications in functional genomics and potential as therapeutics
Dorsett, Y., & Tuschl, T. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1345 · Cited by 917
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
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
Self-citationOrthogonal Cas9 proteins for RNA-guided gene regulation and editing
Esvelt, K. M., Mali, P., Braff, J. L., Moosburner, M., Yaung, S. J., & Church, G. M. (2013) · Nature Methods · doi:10.1038/nmeth.2681 · Cited by 786
Genome-wide analysis reveals characteristics of off-target sites bound by the Cas9 endonuclease
Kuscu, C., Arslan, S., Singh, R., Thorpe, J., & Adli, M. (2014) · Nature Biotechnology · doi:10.1038/nbt.2916 · Cited by 777
In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9
Swiech, L., Heidenreich, M., Banerjee, A., Habib, N., Li, Y., Trombetta, J., Sur, M., & Zhang, F. (2015) · Nature Biotechnology · doi:10.1038/nbt.3055 · Cited by 772
Self-citationCheng, A. W., Wang, H., Yang, H., Shi, L., Yarden Katz, A., Theunissen, T. W., Rangarajan, S., Shivalila, C., Dadon, D. B., & Jaenisch, R. (2013) · Cell Research · doi:10.1038/cr.2013.122 · Cited by 768
Rouet, P., Smih, F., & Jasin, M. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.12.8096 · Cited by 739
High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells
Zhou, Y., Zhu, S., Cai, C., Yuan, P., Li, C., Huang, Y., & Wei, W. (2014) · Nature · doi:10.1038/nature13166 · Cited by 733
Defining functional DNA elements in the human genome
Kellis, M., Wold, B. J., Snyder, M. P., Bernstein, B., Kundaje, A. B., Marinov, G. K., Ward, L. D., Birney, E., Crawford, G. E., Dekker, J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318948111 · Cited by 724
Genome-Wide RNAi Analysis of Growth and Viability in Drosophila Cells
Boutros, M., Kiger, A. A., Armknecht, S., Kerr, K., Hild, M., Koch, B., Haas, S. A., Paro, R., & Perrimon, N. (2004) · Science · doi:10.1126/science.1091266 · Cited by 702
A resource for large-scale RNA-interference-based screens in mammals
Paddison, P. J., Silva, J. M., Conklin, D. S., Schlabach, M., Li, M. Z., Aruleba, S., Balija, V. S., O'Shaughnessy, A., Gnoj, L., Scobie, K., et al. (2004) · Nature Cell Biology · doi:10.1038/nature02370 · Cited by 695
Genome-wide detection of DNA double-stranded breaks induced by engineered nucleases
Frock, R. L., Hu, J., Meyers, R. M., Ho, Y.-J., Kii, E., & Alt, F. W. (2015) · Nature Biotechnology · doi:10.1038/nbt.3101 · Cited by 673
Structural basis for 5′-nucleotide base-specific recognition of guide RNA by human AGO2
Frank, F., Sonenberg, N., & Nagar, B. (2010) · Nature · doi:10.1038/nature09039 · Cited by 666
Determination of Anteroposterior Polarity in Drosophila
Nüsslein‐Volhard, C., Frohnhöfer, H. G., & Lehmann, R. (1987) · Science · doi:10.1126/science.3686007 · Cited by 649
The art and design of genetic screens: Drosophila melanogaster
St Johnston, D. (2002) · Nature Reviews Genetics · doi:10.1038/nrg751 · Cited by 644
Lin, Y., Cradick, T. J., Brown, M. T., Deshmukh, H., Ranjan, P., Sarode, N., Wile, B. M., Vertino, P. M., Stewart, F. J., & Bao, G. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku402 · Cited by 634
Second-generation shRNA libraries covering the mouse and human genomes
Silva, J. M., Li, M. Z., Chang, K. C. N., Ge, W., Golding, M. C., Rickles, R. J., Siolas, D., Hu, G., Paddison, P. J., Schlabach, M. R., et al. (2005) · Nature Genetics · doi:10.1038/ng1650 · Cited by 625
Statistical methods for analysis of high-throughput RNA interference screens
Birmingham, A., Selfors, L. M., Forster, T., Wrobel, D., Kennedy, C. J., Shanks, E., Santoyo-Lopez, J., Dunican, D. J., Long, A., Kelleher, D., et al. (2009) · Nature Methods · doi:10.1038/nmeth.1351 · Cited by 586
A public genome-scale lentiviral expression library of human ORFs
Yang, X., Boehm, J. S., Yang, X., Salehi-Ashtiani, K., Hao, T., Shen, Y., Lubonja, R., Thomas, S. R., Alkan, O., Bhimdi, T., et al. (2011) · Nature Methods · doi:10.1038/nmeth.1638 · Cited by 570
Haploid Genetic Screens in Human Cells Identify Host Factors Used by Pathogens
Carette, J. E., Guimarães, C. P., Varadarajan, M., Park, A. S., Wüthrich, I., Godarova, A., Kotecki, M., Cochran, B., Spooner, E., Ploegh, H. L., et al. (2009) · Science · doi:10.1126/science.1178955 · Cited by 499
The art and design of genetic screens: RNA interference
Boutros, M., & Ahringer, J. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2364 · Cited by 489
Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system
Dupuy, A. J., Akagi, K., Largaespada, D. A., Copeland, N. G., & Jenkins, N. A. (2005) · Nature · doi:10.1038/nature03691 · Cited by 482
Veres, A., Gosis, B. S., Ding, Q., Collins, R., Ragavendran, A., Brand, H., Erdin, S., Cowan, C. A., Talkowski, M. E., & Musunuru, K. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.04.020 · Cited by 474
Synthetic lethal screen identification of chemosensitizer loci in cancer cells
Whitehurst, A. W., Bodemann, B. O., Cardenas, J., Ferguson, D., Girard, L., Peyton, M., Minna, J. D., Michnoff, C. H., Hao, W., Roth, M. G., et al. (2007) · Nature · doi:10.1038/nature05697 · Cited by 471
The art and design of genetic screens: Caenorhabditis elegans
Jørgensen, E. M., & Mango, S. E. (2002) · Nature Reviews Genetics · doi:10.1038/nrg794 · Cited by 440
The art and design of genetic screens: zebrafish
Patton, E. E., & Zon, L. I. (2001) · Nature Reviews Genetics · doi:10.1038/35103567 · Cited by 433
An Oncogenomics-Based In Vivo RNAi Screen Identifies Tumor Suppressors in Liver Cancer
Zender, L., Xue, W., Zuber, J. A., Semighini, C. P., Krasnitz, A., Ma, B., Zender, P., Kubicka, S., Luk, J. M., Schirmacher, P., et al. (2008) · Cell · doi:10.1016/j.cell.2008.09.061 · Cited by 428
Cheung, H. W., Cowley, G. S., Weir, B. A., Boehm, J. S., Rusin, S., Scott, J. A., East, A., Ali, L. D., Lizotte, P. H., Wong, T. C., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1109363108 · Cited by 423
Hoffman, G. R., Rahal, R., Buxton, F., Xiang, K., McAllister, G., Frias, E., Bagdasarian, L., Huber, J., Lindeman, A., Chen, D., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1316793111 · Cited by 421
Antiviral RNA Interference in Mammalian Cells
Maillard, P. V., Ciaudo, C., Marchais, A., Li, Y., Jay, F., Ding, S., & Voinnet, O. (2013) · Science · doi:10.1126/science.1241930 · Cited by 409
High-throughput RNAi screening in cultured cells: a user's guide
Echeverri, C. J., & Perrimon, N. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1836 · Cited by 380
Microhomology-based choice of Cas9 nuclease target sites
Bae, S., Kweon, J., Kim, H. S., & Kim, J. (2014) · Nature Methods · doi:10.1038/nmeth.3015 · Cited by 380
High-throughput RNAi screening by time-lapse imaging of live human cells
Neumann, B., Held, M., Liebel, U., Erfle, H., Rogers, P., Pepperkok, R., & Ellenberg, J. (2006) · Nature Methods · doi:10.1038/nmeth876 · Cited by 380
A Genome-Scale RNA Interference Screen Implicates NF1 Loss in Resistance to RAF Inhibition
Whittaker, S. R., Theurillat, J.-P. P., Allen, E. M. V., Wagle, N., Hsiao, J., Cowley, G. S., Schadendorf, D., Root, D. E., & Garraway, L. A. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0470 · Cited by 369
RNA Interference Functions as an Antiviral Immunity Mechanism in Mammals
Li, Y., Lü, J., Han, Y., Fan, X., & Ding, S. (2013) · Science · doi:10.1126/science.1241911 · Cited by 365
High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy
Hasson, S. A., Kane, L. A., Yamano, K., Huang, C.-H., Sliter, D. A., Buehler, E., Wang, C., Heman-Ackah, S. M., Hessa, T., Guha, R., et al. (2013) · Nature · doi:10.1038/nature12748 · Cited by 365
A Systematic Mammalian Genetic Interaction Map Reveals Pathways Underlying Ricin Susceptibility
Bassik, M. C., Kampmann, M., Lebbink, R. J., Wang, S., Hein, M. Y., Poser, I., Weibezahn, J., Horlbeck, M. A., Chen, S., Mann, M., et al. (2013) · Cell · doi:10.1016/j.cell.2013.01.030 · Cited by 365
Genome-scale loss-of-function screening with a lentiviral RNAi library
Root, D. E., Hacohen, N., Hahn, W. C., Lander, E. S., & Sabatini, D. M. (2006) · Nature Methods · doi:10.1038/nmeth924 · Cited by 364
Rouet, P., Smih, F., & Jasin, M. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.12.8096-8106.1994 · Cited by 363
Saturation editing of genomic regions by multiplex homology-directed repair
Findlay, G. M., Boyle, E. A., Hause, R. J., Klein, J. C., & Shendure, J. (2014) · Nature · doi:10.1038/nature13695 · Cited by 362
Ketting, R. F. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.01.012 · Cited by 353
A genetic screen for mutations affecting embryogenesis in zebrafish.
Driever, W., Solnica‐Krezel, L., Schier, A. F., Neuhauss, S. C. F., Malicki, J. J., Stemple, D. L., Stainier, D. Y. R., Zwartkruis, F. J. T., Abdelilah, S., Rangini, Z., et al. (1996) · Zurich Open Repository and Archive (University of Zurich) · doi:10.5167/uzh-215 · Cited by 349
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
Smith, C., Gore, A., Yan, W., Abalde-Atristain, L., Li, Z., He, C., Wang, Y., Brodsky, R. A., Zhang, K., Cheng, L., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.06.011 · Cited by 342
LeProust, E. M., Peck, B. J., Spirin, K., McCuen, H. B., Moore, B., Namsaraev, E., & Caruthers, M. H. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq163 · Cited by 326
The Loop Position of shRNAs and Pre-miRNAs Is Critical for the Accuracy of Dicer Processing In Vivo
Gu, S., Jin, L., Zhang, Y., Huang, Y., Zhang, F., Valdmanis, P. N., & Kay, M. A. (2012) · Cell · doi:10.1016/j.cell.2012.09.042 · Cited by 291
Self-citationIn vivo RNAi screening identifies a mechanism of sorafenib resistance in liver cancer
Rudalska, R., Dauch, D., Longerich, T., McJunkin, K., Wuestefeld, T., Kang, T.-W., Hohmeyer, A., Pesic, M., Leibold, J., von Thun, A., et al. (2014) · Nature Medicine · doi:10.1038/nm.3679 · Cited by 282
Lessons from Nature: microRNA-based shRNA libraries
Chang, K., Elledge, S. J., & Hannon, G. J. (2006) · Nature Methods · doi:10.1038/nmeth923 · Cited by 280
A computational study of off-target effects of RNA interference
Qiu, S. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki324 · Cited by 276
Direct in Vivo RNAi Screen Unveils Myosin IIa as a Tumor Suppressor of Squamous Cell Carcinomas
Schramek, D., Sendoel, A., Segal, J. P., Beronja, S., Heller, E., Oristian, D., Reva, B. A., & Fuchs, E. V. (2014) · Science · doi:10.1126/science.1248627 · Cited by 269
The art and design of genetic screens: yeast
Forsburg, S. L. (2001) · Nature Reviews Genetics · doi:10.1038/35088500 · Cited by 265
Single-Molecule mRNA Decay Measurements Reveal Promoter- Regulated mRNA Stability in Yeast
Trcek, T., Larson, D. R., Moldón, A., Query, C. C., & Singer, R. H. (2011) · Cell · doi:10.1016/j.cell.2011.11.051 · Cited by 261
The art and design of genetic screens: Arabidopsis thaliana
Page, D. R., & Grossniklaus, U. (2002) · Nature Reviews Genetics · doi:10.1038/nrg730 · Cited by 240
In vivo discovery of immunotherapy targets in the tumour microenvironment
Zhou, P., Shaffer, D. R., Alvarez Arias, D. A., Nakazaki, Y., Pos, W., Torres, A. J., Cremasco, V., Dougan, S. K., Cowley, G. S., Elpek, K., et al. (2014) · Nature · doi:10.1038/nature12988 · Cited by 237
Using next-generation sequencing to isolate mutant genes from forward genetic screens
Schneeberger, K. (2014) · Nature reviews genetics · doi:10.1038/nrg3745 · Cited by 233
PiggyBac Transposon Mutagenesis: A Tool for Cancer Gene Discovery in Mice
Rad, R., Rad, L., Wang, W., Cadiñanos, J., Vassiliou, G. S., Rice, S., Campos, L. S., Yusa, K., Banerjee, R., Li, M. A., et al. (2010) · Science · doi:10.1126/science.1193004 · Cited by 230
Building mammalian signalling pathways with RNAi screens
Moffat, J., & Sabatini, D. M. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1860 · Cited by 204
The love–hate relationship between Ras and NotchPreprint
Sundaram, M. V. (2005) · Genes & Development · doi:10.1101/gad.1330605 · Cited by 191
Promoter Elements Regulate Cytoplasmic mRNA Decay
Bregman, A., Avraham‐Kelbert, M., Barkai, O., Duek, L., Guterman, A., & Choder, M. (2011) · Cell · doi:10.1016/j.cell.2011.12.005 · Cited by 181
RNAi screens in mice identify physiological regulators of oncogenic growth
Beronja, S., Janki, P., Heller, E., Lien, W., Keyes, B. E., Oshimori, N., & Fuchs, E. V. (2013) · Nature · doi:10.1038/nature12464 · Cited by 162
Harnessing transposons for cancer gene discovery
Copeland, N. G., & Jenkins, N. A. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2916 · Cited by 155
Isolation and Characterization of a Near-Haploid Human Cell Line
Kotecki, M. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4656 · Cited by 155
Mismatch repair genes identified using genetic screens in Blm-deficient embryonic stem cells
Guo, G., Wang, W., & Bradley, A. (2004) · Nature · doi:10.1038/nature02653 · Cited by 135
Repurposing CRISPR/Cas9 for in situ functional assaysPreprint
Malina, A., Mills, J. R., Cencic, R., Yan, Y., Fraser, J., Nederveen-Schippers, L. M., Paquet, M., Dostie, J., & Pelletier, J. (2013) · Genes & Development · doi:10.1101/gad.227132.113 · Cited by 132
Harnessing transposons for cancer gene discovery
Neal, Copeland, Nancy, N., & Jenkins (2007) · 南京医科大学学报:英文版 · Cited by 128
Quantifying Genome-Editing Outcomes at Endogenous Loci with SMRT Sequencing
Hendel, A., Kildebeck, E., Fine, E. J., Clark, J. T., Punjya, N., Sebastiano, V., Bao, G., & Porteus, M. H. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.02.040 · Cited by 124
Production of complex nucleic acid libraries using highly parallel in situ oligonucleotide synthesis
Cleary, M. A., Kilian, K. A., Wang, Y., Bradshaw, J., Cavet, G., Ge, W., Kulkarni, A., Paddison, P. J., Chang, K., Sheth, N. U., et al. (2004) · Nature Methods · doi:10.1038/nmeth724 · Cited by 108
The art and design of genetic screens: mammalian culture cells
Grimm, S. (2004) · Nature reviews genetics · doi:10.1038/nrg1291 · Cited by 107
The art and design of genetic screens: mouse
Kile, B. T., & Hilton, D. J. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1636 · Cited by 104
Rapid creation and quantitative monitoring of high coverage shRNA libraries
Bassik, M. C., Lebbink, R. J., Churchman, L. S., Ingolia, N. T., Patena, W., LeProust, E. M., Schuldiner, M., Weissman, J. S., & McManus, M. T. (2009) · Nature Methods · doi:10.1038/nmeth.1330 · Cited by 99
The art and design of genetic screens: Escherichia coli
Shuman, H. A., & Silhavy, T. J. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1087 · Cited by 99
Franceschini, A., Meier, R., Casanova, A., Kreibich, S., Daga, N., Andritschke, D., Dilling, S., Rämö, P., Emmenlauer, M., Kaufmann, A. M., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402353111 · Cited by 70
siRNA off-target effects in genome-wide screens identify signaling pathway members
Buehler, E., Khan, A. A., Marine, S. D., Rajaram, M., Bahl, A., Burchard, J., & Ferrer, M. (2012) · Scientific Reports · doi:10.1038/srep00428 · Cited by 69
A dynamic perspective of RNAi library development
Pan, Q., van der Laan, L. J. W., Janssen, H. L. A., & Peppelenbosch, M. P. (2012) · Trends in biotechnology · doi:10.1016/j.tibtech.2012.01.002 · Cited by 28
Zhong, R., Kim, J., Kim, H. S., Kim, M., Lum, L., Levine, B., Xiao, G., White, M. A., & Xie, Y. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku306 · Cited by 22
Burgess, D. J. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3616 · Cited by 5
Flagged first, then by citations
Cited by
Sorted by citations
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
The Biogenesis, Functions, and Challenges of Circular RNAs
Li, X., Yang, L. C., & Chen, L. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.06.034 · Cited by 2,060
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
Oughtred, R., Rust, J., Chang, C., Breitkreutz, B., Stark, C., Willems, A., Boucher, L., Leung, G., Kolas, N., Zhang, F., et al. (2021) · Protein Science · doi:10.1002/pro.3978 · Cited by 1,858
Self-citationLi, H., Yang, Y., Hong, W., Huang, M., Wu, M., & Zhao, X. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0089-y · Cited by 1,829
Metadata
- Authors
- Shalem, O., Sanjana, N. E., & Zhang, F.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Shalem, Ophir
- Zhang, Feng
- Venue
- Nature Reviews Genetics
- Published
- 2015-04-09
- Volume
- 16
- Issue
- 5
- Pages
- 299-311
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- PMC
- PMC4503232
- OpenAlex
- W2026592619
- Cited by
- 1,233
- References
- 130
- Citations by year
- 2026: 71 · 2025: 91 · 2024: 103 · 2023: 85 · 2022: 101 · 2021: 105 · 2020: 121 · 2019: 117 · 2018: 131 · 2017: 145 · 2016: 123 · 2015: 37
- FWCI
- 14.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- PMC
- Funders
- Klarman Family Foundation
- Simons Center for the Social Brain, Massachusetts Institute of Technology
- National Institute of Mental Health (DP1MH100706)
- National Human Genome Research Institute (K99HG008171)
- National Institute of Neurological Disorders and Stroke (R01NS073124)
- National Center for Chronic Disease Prevention and Health Promotion (DP1‑MH100706)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- CRISPR/Cas9, genome-wide screen, guide RNA library, forward genetic screen, gene knockout, transcriptional regulation, phenotypic screening, screen design, functional genomics
- MeSH terms
- Animals, Genetic Testing, Humans, Models, Genetic, Gene Library, Genomics, RNA Interference, Mice, Gene Knockout Techniques, High-Throughput Nucleotide Sequencing, 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