Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation
Open accessAbstract
While the catalog of mammalian transcripts and their expression levels in different cell types and disease states is rapidly expanding, our understanding of transcript function lags behind. We present a robust technology enabling systematic investigation of the cellular consequences of repressing or inducing individual transcripts. We identify rules for specific targeting of transcriptional repressors (CRISPRi), typically achieving 90%-99% knockdown with minimal off-target effects, and activators (CRISPRa) to endogenous genes via endonuclease-deficient Cas9. Together they enable modulation of gene expression over a ∼1,000-fold range. Using these rules, we construct genome-scale CRISPRi and CRISPRa libraries, each of which we validate with two pooled screens. Growth-based screens identify essential genes, tumor suppressors, and regulators of differentiation. Screens for sensitivity to a cholera-diphtheria toxin provide broad insights into the mechanisms of pathogen entry, retrotranslocation and toxicity. Our results establish CRISPRi and CRISPRa as powerful tools that provide rich and complementary information for mapping complex pathways.
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
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?
Compared with gain-of-function perturbations, a higher proportion of loss-of-function perturbations yield phenotypes in growth and chemical-genetic screens, especially for members of protein complexes.
“Compared with gain-of-function perturbations, a higher proportion of loss-of-function perturbations yield phenotypes in growth and chemical-genetic screens, especially for members of protein complexes (Gilbert et al., 2014; Horlbeck et al., 2016).”
From Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq (2022) · cites this paper as Gilbert et al., 2014
In Results, “A Genome-Scale CRISPRa Screening Platform” reports that fewer CRISPRa sgRNAs than CRISPRi sgRNAs caused growth phenotypes. The ricin-screen Results likewise report phenotypes for all genes selected for a prior knockdown phenotype, but only a subset upon activation. The toxin-screen Results identify protein-complex members as CRISPRi hits, but do not establish that loss-of-function perturbations yield a higher proportion of hits than gain-of-function perturbations in chemical-genetic screens, especially for those members. Page numbers are unavailable in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredCRISPRi and CRISPRa technologies utilize catalytically inactive Cas9 (dCas9) fused to either a transcriptional repressor (e.g., KRAB) or a transcriptional activator (e.g., VPR).
“For example, CRISPRi (interference)23–25 and CRISPRa (activation)26–30 technologies utilize catalytically inactive Cas9 (dCas9) fused to either a transcriptional repressor (e.g., KRAB, Krüppel associated box) or a transcriptional activator (e.g., VPR, VP64-p65-Rta).”
From Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions (2025) · cites this paper as [28]
The Introduction describes dCas9 fusion proteins used to repress transcription (CRISPRi) or activate it (CRISPRa), and the CRISPRi Results identify KRAB as a repressor domain. The CRISPRa Results describe a sunCas9 system that recruits activating effector domains, but do not identify VPR (VP64-p65-Rta) as its activator or describe a dCas9–VPR fusion. No page numbers are available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAlternatives to DNA cleavage-induced editing include base editing, prime editing, and CRISPRi/CRISPRa.
“Alternatives to DNA cleavage-induced editing include using CRISPR-Cas9 for direct chemical sequence alteration (base editing) 25,26 , providing RNA templates for gene alteration (prime editing) 27,28 , and for transcriptional control (CRISPR interference, CRISPRi; CRISPR activation, CRISPRa) 29,30 (Fig. 3).”
From The promise and challenge of therapeutic genome editing (2020) · cites this paper as [30]
Experimental — accuracy not yet measuredPooling gene perturbations increases scalability but cannot be combined with imaging of complex or dynamic cellular phenotypes.
“Pooling gene perturbations greatly improves scalability, but is not compatible with imaging of complex and dynamic cellular phenotypes.”
From Optical Pooled Screens in Human Cells (2019) · cites this paper as Gilbert et al., 2014
Mutations in ubiquitously expressed trafficking factors or aminoacyl-tRNA synthetases can cause neurodegenerative diseases such as Charcot-Marie-Tooth disease.
“Striking examples are familial mutations causing neurodegenerative diseases, such as hereditary motor and sensory neuropathies (Charcot-Marie-Tooth disease), which can be caused by mutations in ubiquitously expressed trafficking factors (RAB7A, DNM2, DYNC1H1), or aminoacyl-tRNA synthetases (AARS, GARS, HARS, MARS)2.”
From Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis (2021) · cites this paper as [2]
Gene function can be cell-type specific, as shown by mutations in broadly expressed genes causing cell-type specific defects and disease.
“In addition to gene expression, gene function can also be cell type-specific, as evidenced by the fact that mutations in broadly expressed or housekeeping genes can lead to cell-type specific defects and disease states.”
From Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis (2021) · cites this paper as [2]
CRISPRa assesses gain-of-function phenotypes and can complement CRISPR knockout or CRISPRi loss-of-function screens.
“CRISPRa evaluates gain-of-function phenotypes and can provide complementary insight to CRISPR knockout or CRISPRi-based loss-of-function screens42.”
From CRISPR-based functional genomics for neurological disease (2020) · cites this paper as [42]
CRISPRi knockdown is non-toxic in iPSCs and iPSC-derived cells, inducible, and reversible, enabling time-resolved analysis of gene function.
“CRISPRi-based gene knockdown may result in weaker phenotypes than full gene knockout, however it is non-toxic in iPSCs and iPSC-derived cells76, inducible76 and reversible42, thereby enabling time-resolved analysis of gene function76.”
From CRISPR-based functional genomics for neurological disease (2020) · cites this paper as [42]
CRISPRi avoids the widespread off-target effects that are intrinsic to RNAi-based screening.
“CRISPRi represents an important advance over RNAi, since it lacks the pervasive off-target effects (Gilbert et al., 2014) inherent to RNAi-based screening approaches (Adamson et al., 2012; Jackson et al., 2003; Kaelin, 2012).”
From CRISPR Interference-Based Platform for Multimodal Genetic Screens in Human iPSC-Derived Neurons (2019) · cites this paper as Gilbert et al., 2014
CRISPR interference is inducible and reversible.
“Second, it is inducible and reversible (Gilbert et al., 2014)”
From CRISPR Interference-Based Platform for Multimodal Genetic Screens in Human iPSC-Derived Neurons (2019) · cites this paper as Gilbert et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673 · see citing works
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 · see citing works
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn923 · Cited by 14,108 · see citing works
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013) · Science · doi:10.1126/science.1235122 · Cited by 7,863 · 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
Landscape of transcription in human cells
Djebali, S., Davis, C. A., Merkel, A., Dobin, A., Lassmann, T., Mortazavi, A., Tanzer, A., Lagarde, J., Lin, W., Schlesinger, F., et al. (2012) · Nature · doi:10.1038/nature11233 · Cited by 5,187 · see citing works
Derrien, T., Johnson, R., Bussotti, G., Andrea Tanzer, A., Djebali, S., Tilgner, H., Guernec, G., Martin, D., Merkel, A., Knowles, D. G., et al. (2012) · Genome Research · doi:10.1101/gr.132159.111 · Cited by 5,017 · see citing works
Repurposing 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
Self-citationDNA 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
ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering
Gaj, T., Gersbach, C. A., & Barbas, C. F. (2013) · Trends in Biotechnology · doi:10.1016/j.tibtech.2013.04.004 · Cited by 3,820 · 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
Self-citationExpression of a single transfected cDNA converts fibroblasts to myoblasts
Davis, R. L., Weintraub, H. M., & Lassar, A. B. (1987) · Cell · doi:10.1016/0092-8674(87)90585-x · Cited by 3,388 · 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
CRISPR-Cas systems for editing, regulating and targeting genomes
Sander, J. D., & Joung, J. K. (2014) · Nature Biotechnology · doi:10.1038/nbt.2842 · Cited by 3,153 · 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
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 · see citing works
The Noncoding RNA Revolution—Trashing Old Rules to Forge New Ones
Cech, T. R., & Steitz, J. A. (2014) · Cell · doi:10.1016/j.cell.2014.03.008 · Cited by 2,270 · see citing works
Transcription factors: from enhancer binding to developmental control
Spitz, F., & Furlong, E. E. M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3207 · Cited by 2,227 · see citing works
The Genetic Landscape of a Cell
Costanzo, M., Baryshnikova, A., Bellay, J., Kim, Y., Spear, E. D., Sevier, C. S., Ding, H., Koh, J. L. Y., Toufighi, K., Mostafavi, S., et al. (2010) · Science · doi:10.1126/science.1180823 · Cited by 2,162 · see citing works
Self-citationDynamic 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 1,931 · see citing works
Self-citationA 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 1,559 · see citing works
Self-citationRNA in unexpected places: long non-coding RNA functions in diverse cellular contexts
Geisler, S., & Coller, J. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3679 · Cited by 1,451 · see citing works
Sensing and repairing DNA double-strand breaks
Jackson, S. P. (2002) · Carcinogenesis · doi:10.1093/carcin/23.5.687 · Cited by 1,126 · see citing works
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 · 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
Davoli, T., Xu, A. W., Mengwasser, K. E., Sack, L. M., Yoon, J. C., Park, P. J., & Elledge, S. J. (2013) · Cell · doi:10.1016/j.cell.2013.10.011 · Cited by 815 · see citing works
The Polo kinase Plk4 functions in centriole duplication
Habedanck, R., Stierhof, Y., Wilkinson, C. J., & Nigg, E. A. (2005) · Nature Cell Biology · doi:10.1038/ncb1320 · Cited by 809 · see citing works
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 · see citing works
Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription
Zhang, F., Cong, L., Lodato, S., Kosuri, S., Church, G. M., & Arlotta, P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1775 · Cited by 771 · see citing works
Retrograde transport from endosomes to the trans-Golgi network
Bonifacino, J. S., & Rojas, R. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1985 · Cited by 668 · see citing works
Exploring genetic interactions and networks with yeast
Boone, C., Bussey, H., & Andrews, B. J. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2085 · Cited by 661 · see citing works
Beerli, R. R., Segal, D. J., Dreier, B., & Barbas, C. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14628 · Cited by 539 · see citing works
Haploid Genetic Screens in Human Cells Identify Host Factors Used by Pathogens
Carette, J., Guimarães, C. P., Varadarajan, M., Park, A. S., Wuethrich, I., Godarova, A., Kotecki, M., Cochran, B., Spooner, E., Ploegh, H., et al. (2009) · Science · doi:10.1126/science.1178955 · Cited by 508 · see citing works
Self-citationAdamson, B., Smogorzewska, A., Sigoillot, F. D., King, R. W., & Elledge, S. J. (2012) · Nature Cell Biology · doi:10.1038/ncb2426 · Cited by 433 · see citing works
Self-citationHuang, L. C., Clarkin, K. C., & Wahl, G. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.10.4827 · Cited by 384 · see citing works
PU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding
Zhang, P., Zhang, X., Iwama, A., Yu, C., Smith, K. A., Mueller, B. U., Narravula, S., Torbett, B. E., Orkin, S. H., & Tenen, D. G. (2000) · Blood · doi:10.1182/blood.v96.8.2641 · Cited by 368 · see citing works
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 · see citing works
Self-citationPositive and negative regulation of endogenous genes by designed transcription factors
Beerli, R. R., Dreier, B., & Barbas, C. F. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.040552697 · Cited by 349 · see citing works
Considerations when investigating lncRNA function in vivo
Bassett, A. R., Akhtar, A., Barlow, D. P., Bird, A. P., Brockdorff, N., Duboule, D., Ephrussi, A., Ferguson‐Smith, A. C., Gingeras, T., Haerty, W., et al. (2014) · eLife · doi:10.7554/elife.03058 · Cited by 348 · see citing works
TSGene: a web resource for tumor suppressor genes
Zhao, M., Sun, J., & Zhao, Z. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks937 · Cited by 325 · see citing works
Lessons from Nature: microRNA-based shRNA libraries
Chang, K., Elledge, S. J., & Hannon, G. J. (2006) · Nature Methods · doi:10.1038/nmeth923 · Cited by 283 · see citing works
Targeted selection of recombinant clones through gene dosage effects.
Rine, J., Hansen, W., Hardeman, E. C., & Davis, R. W. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.22.6750 · Cited by 252 · see citing works
APPRIS: annotation of principal and alternative splice isoforms
Rodriguez, J. M., Maietta, P., Ezkurdia, I., Pietrelli, A., Wesselink, J.-J., Lopez, G., Valencia, A., & Tress, M. L. (2013) · Nucleic Acids Research · doi:10.1093/nar/gks1058 · Cited by 232 · see citing works
Ness, B. G. V., Howard, J. B., & Bodley, J. W. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)70366-4 · Cited by 225 · see citing works
Cholera Toxin: An Intracellular Journey into the Cytosol by Way of the Endoplasmic Reticulum
Wernick, N. L. B., Chinnapen, D. J. ‐., Cho, J. A., & Lencer, W. I. (2010) · Toxins · doi:10.3390/toxins2030310 · Cited by 215 · see citing works
Recurrent Hemizygous Deletions in Cancers May Optimize Proliferative Potential
Solimini, N. L., Xu, Q., Mermel, C. H., Liang, A. C. T., Schlabach, M. R., Luo, J., Burrows, A. E., Anselmo, A. N., Bredemeyer, A. L., Li, M. Z., et al. (2012) · Science · doi:10.1126/science.1219580 · Cited by 211 · see citing works
A bioinformatics method identifies prominent off-targeted transcripts in RNAi screens
Sigoillot, F. D., Lyman, S. K., Huckins, J. F., Adamson, B., Chung, E., Quattrochi, B., & King, R. W. (2012) · Nature Methods · doi:10.1038/nmeth.1898 · Cited by 159 · see citing works
Self-citationA novel docking site on Mediator is critical for activation by VP16 in mammalian cells
Mittler, G., Stühler, T., Santolin, L., Uhlmann, T., Kremmer, E., Lottspeich, F., Berti, L., & Meisterernst, M. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg619 · Cited by 152 · see citing works
Tanenbaum, M. E., Macurek, L., van der Vaart, B., Galli, M., Akhmanova, A., & Medema, R. H. (2011) · Current Biology · doi:10.1016/j.cub.2011.07.017 · Cited by 148 · see citing works
Genome-wide identification of CRISPR/Cas9 off-targets in human genome
Duan, J., Lu, G., Xie, Z., Lou, M., Luo, J., Guo, L., & Zhang, Y. (2014) · Cell Research · doi:10.1038/cr.2014.87 · Cited by 137 · see citing works
Kampmann, M., Bassik, M. C., & Weissman, J. S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1307002110 · Cited by 123 · see citing works
Self-citationDerlin-1 Facilitates the Retro-Translocation of Cholera Toxin
Bernardi, K. M., Forster, M. L., Lencer, W. I., & Tsai, B. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-08-0755 · Cited by 112 · see citing works
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 · see citing works
Self-citationKampmann, M., Bassik, M. C., & Weissman, J. S. (2014) · Nature Protocols · doi:10.1038/nprot.2014.103 · Cited by 87 · see citing works
Self-citationSmith, R. D., Willett, R. A., Kudlyk, T. A., Pokrovskaya, I. D., Paton, A. W., Paton, J. C., & Lupashin, V. V. (2009) · Traffic · doi:10.1111/j.1600-0854.2009.00965.x · Cited by 77 · see citing works
Identification of host cell factors required for intoxication through use of modified cholera toxin
Guimarães, C. P., Carette, J. E., Varadarajan, M., Antos, J. M., Popp, M. W., Spooner, E., Brummelkamp, T. R., & Ploegh, H. L. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201108103 · Cited by 66 · see citing works
Self-citationC/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia
Alberich-Jordà, M., Wouters, B. J., Balaštík, M., Shapiro-Koss, C., Zhang, H., Ruscio, A. D., Radomska, H. S., Ebralidze, A. K., Amabile, G., Ye, M., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci65102 · Cited by 59 · see citing works
X Inactivation in Mouse ES Cells: Histone Modifications and FISH
Panning, B. (2003) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(03)76028-5 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9
Doench, J. G., Fusi, N., Sullender, M., Hegde, M., Vaimberg, E. W., Donovan, K. F., Smith, I., Tothova, Z., Wilen, C., Orchard, R., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3437 · Cited by 4,637 · 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
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 · 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 integrated stress response: From mechanism to disease
Costa-Mattioli, M., & Walter, P. (2020) · Science · doi:10.1126/science.aat5314 · Cited by 1,617 · see citing works
Integrative single-cell analysis
Stuart, T., & Satija, R. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0093-7 · Cited by 1,460 · see citing works
High-Throughput Sequencing Technologies
Reuter, J., Spacek, D. V., & Snyder, M. P. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.05.004 · Cited by 1,330 · see citing works
Genome-scale CRISPR-Cas9 Knockout and Transcriptional Activation Screening
Joung, J., Konermann, S., Gootenberg, J. S., Abudayyeh, O. O., Platt, R. J., Brigham, M. D., Sanjana, N. E., & Zhang, F. (2017) · Nature Protocols · doi:10.1038/nprot.2017.016 · Cited by 1,243 · see citing works
ceRNA in cancer: possible functions and clinical implications
Qi, X., Zhang, D., Wu, N., Xiao, J., Wang, X., & Ma, W. (2015) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2015-103334 · Cited by 1,267 · see citing works
Transcriptome Engineering with RNA-Targeting Type VI-D CRISPR Effectors
Konermann, S., Lotfy, P., Brideau, N. J., Oki, J., Shokhirev, M. N., & Hsu, P. D. (2018) · Cell · doi:10.1016/j.cell.2018.02.033 · Cited by 1,164 · 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
Adamson, 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
Self-citationDelivering CRISPR: a review of the challenges and approaches
Lino, C. A., Harper, J. C., Carney, J. P., & Timlin, J. A. (2018) · Drug Delivery · doi:10.1080/10717544.2018.1474964 · Cited by 1,185 · see citing works
The promise and challenge of therapeutic genome editing
Doudna, J. A. (2020) · Nature · doi:10.1038/s41586-020-1978-5 · Cited by 1,126 · see citing works
Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells
Hendel, A., Bak, R. O., Clark, J. T., Kennedy, A. B., Ryan, D. E., Roy, S., Steinfeld, I., Lunstad, B. D., Kaiser, R. J., Wilkens, A. B., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3290 · Cited by 1,090 · 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
Self-citationOptimized libraries for CRISPR-Cas9 genetic screens with multiple modalities
Sanson, K. R., Hanna, R. E., Hegde, M., Donovan, K. F., Strand, C., Sullender, M. E., Vaimberg, E. W., Goodale, A., Root, D. E., Piccioni, F., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07901-8 · Cited by 1,043 · see citing works
Horlbeck, M. A., Gilbert, L. A., Villalta, J. E., Adamson, B., Pak, R. A., Chen, Y., Fields, A. P., Park, C. Y., Corn, J. E., Kampmann, M., et al. (2016) · eLife · doi:10.7554/elife.19760 · Cited by 894 · see citing works
Self-citationCRISPR-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 1,011 · see citing works
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 · 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
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
Self-citationGenome-wide CRISPR Screen in a Mouse Model of Tumor Growth and Metastasis
Chen, S., Sanjana, N. E., Zheng, K., Shalem, O., Lee, K., Shi, X., Scott, D. A., Song, J. W., Pan, J. Q., Weissleder, R., et al. (2015) · Cell · doi:10.1016/j.cell.2015.02.038 · Cited by 891 · see citing works
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 · see citing works
Self-citationEnhanced prime editing systems by manipulating cellular determinants of editing outcomes
Chen, P. J., Hussmann, J. A., Yan, J., Knipping, F., Ravisankar, P., Chen, P.-F., Chen, C.-D., Nelson, J. W., Newby, G. A., Şahin, M., et al. (2021) · Cell · doi:10.1016/j.cell.2021.09.018 · Cited by 820 · see citing works
Self-citationCrystal 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
Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing
Nuñez, J. K., Chen, J., Pommier, G. C., Cogan, J. Z., Replogle, J. M., Adriaens, C., Ramadoss, G. N., Shi, Q., Hung, K. L., Samelson, A. J., et al. (2021) · Cell · doi:10.1016/j.cell.2021.03.025 · Cited by 760 · see citing works
Self-citationOff-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials
Lin, A., Giuliano, C. J., Palladino, A. C., John, K. M., Abramowicz, C., Yuan, M. L., Sausville, E. L., Lukow, D. A., Liu, L., Chait, A. R., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aaw8412 · Cited by 747 · see citing works
Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq
Replogle, J. M., Saunders, R. A., Pogson, A. N., Hussmann, J. A., Lenail, A., Guna, A., Mascibroda, L., Wagner, E. J., Adelman, K., Lithwick-Yanai, G., et al. (2022) · Cell · doi:10.1016/j.cell.2022.05.013 · Cited by 751 · see citing works
Self-citationCRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells
Liu, S. J., Horlbeck, M. A., Cho, S. W., Birk, H. S., Malatesta, M., He, D. X., Attenello, F. J., Villalta, J. E., Cho, M. Y., Chen, Y., et al. (2016) · Science · doi:10.1126/science.aah7111 · Cited by 735 · see citing works
Self-citationA Comprehensive, CRISPR-based Functional Analysis of Essential Genes in Bacteria
Peters, J. M., Colavin, A., Shi, H., Czarny, T. L., Larson, M. H., Wong, S. S., Hawkins, J. S., Lu, C. H. S., Koo, B., Marta, E., et al. (2016) · Cell · doi:10.1016/j.cell.2016.05.003 · Cited by 716 · see citing works
Self-citationMitochondrial stress is relayed to the cytosol by an OMA1–DELE1–HRI pathway
Guo, X., Aviles, G., Liu, Y., Tian, R., Unger, B. A., Lin, Y.-H. T., Wiita, A. P., Xu, K., Correia, M. A., & Kampmann, M. (2020) · Nature · doi:10.1038/s41586-020-2078-2 · Cited by 674 · see citing works
Self-citationA 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
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
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
Synthetic lethality and cancer
O’Neil, N. J., Bailey, M. L., & Hieter, P. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.47 · Cited by 658 · see citing works
Pervasive functional translation of noncanonical human open reading frames
Chen, J., Brunner, A., Cogan, J. Z., Nuñez, J. K., Fields, A. P., Adamson, B., Itzhak, D. N., Li, J. Y., Mann, M., Leonetti, M. D., et al. (2020) · Science · doi:10.1126/science.aay0262 · Cited by 654 · see citing works
Self-citationSystematic mapping of functional enhancer–promoter connections with CRISPR interference
Fulco, C. P., Munschauer, M., Anyoha, R., Munson, G., Grossman, S. R., Perez, E. M., Kane, M., Cleary, B., Lander, E. S., & Engreitz, J. M. (2016) · Science · doi:10.1126/science.aag2445 · Cited by 643 · see citing works
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 · see citing works
Wang, T., Yu, H., Hughes, N. W., Liu, B., Kendirli, A., Klein, K., Chen, W. W., Lander, E. S., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.01.013 · Cited by 632 · see citing works
CRISPR Interference-Based Platform for Multimodal Genetic Screens in Human iPSC-Derived Neurons
Tian, R., Gachechiladze, M. A., Ludwig, C. H., Laurie, M. T., Hong, J. Y., Nathaniel, D., Prabhu, A. V., Fernandopulle, M. S., Patel, R., Abshari, M., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.07.014 · Cited by 543 · see citing works
Self-citationTherapeutic Targeting of Long Non-Coding RNAs in Cancer
Arun, G., Diermeier, S. D., & Spector, D. L. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.01.001 · Cited by 612 · see citing works
Past, 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 · see citing works
Ratti, M., Lampis, A., Ghidini, M., Salati, M., Mirchev, M. B., Valeri, N., & Hahne, J. C. (2020) · Targeted Oncology · doi:10.1007/s11523-020-00717-x · Cited by 608 · see citing works
Epigenetics and epigenomics in diabetic kidney disease and metabolic memory
Kato, M. V., & Natarajan, R. D. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0135-6 · Cited by 604 · see citing works
A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain
Kleaveland, B., Shi, C. Y., Stefano, J., & Bartel, D. P. (2018) · Cell · doi:10.1016/j.cell.2018.05.022 · Cited by 594 · see citing works
Carvacrol and human health: A comprehensive review
Sharifi‐Rad, M., Varoni, E. M., Iriti, M., Martorell, M., Setzer, W. N., Contreras, M. D. M., Salehi, B., Soltani‐Nejad, A., Rajabi, S., Tajbakhsh, M., et al. (2018) · Phytotherapy Research · doi:10.1002/ptr.6103 · Cited by 611 · see citing works
Bock, C., Datlinger, P., Chardon, F. M., Coelho, M. A., Dong, M. B., Lawson, K. A., Lu, T., Maroc, L., Norman, T. M., Song, B., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00093-4 · Cited by 591 · see citing works
Self-citationGenomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting
Aguirre, A. J., Meyers, R. M., Weir, B. A., Vázquez, F., Zhang, C., Ben‐David, U., Cook, A., Ha, G., Harrington, W. F., Doshi, M. B., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0154 · Cited by 565 · see citing works
Liu, Q., Gao, R., Li, J., Lin, L., Zhao, J., Sun, W., & Tian, C. (2017) · Biotechnology for Biofuels · doi:10.1186/s13068-016-0693-9 · Cited by 577 · see citing works
Genome-wide CRISPR Screens in Primary Human T Cells Reveal Key Regulators of Immune Function
Shifrut, E., Carnevale, J., Tobin, V., Roth, T. L., Woo, J. M., Bui, C. T., Li, P. J., Diolaiti, M. E., Ashworth, A., & Marson, A. (2018) · Cell · doi:10.1016/j.cell.2018.10.024 · Cited by 573 · see citing works
Hurtado, S., Milem, J. F., Clayton-Pedersen, A. R., & Allen, W. R. (1999) · Cited by 568 · see citing works
CRISPR Interference Efficiently Induces Specific and Reversible Gene Silencing in Human iPSCs
Mandegar, M. A., Huebsch, N., Frolov, E. B., Shin, E., Truong, A., Olvera, M. P., Chan, A. H., Miyaoka, Y., Holmes, K., Spencer, C. I., et al. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.01.022 · Cited by 525 · see citing works
“Furthermore, some groups have used genome-scale screens with CRISPRi and CRISPR activation (CRISPRa) to identify known and novel genes that control cell growth and sensitivity to cholera-diphtheria toxin (Gilbert et al., 2014).”
InfluentialSelf-citationRibosome profiling reveals the what, when, where and how of protein synthesis
Brar, G. A., & Weissman, J. S. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4069 · Cited by 534 · see citing works
Self-citationTDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A
Brown, A., Wilkins, O. G., Keuss, M. J., Kargbo-Hill, S. E., Zanovello, M., Lee, W. C., Bampton, A., Lee, F. C. Y., Masino, L., Qi, Y. A., et al. (2022) · Nature · doi:10.1038/s41586-022-04436-3 · Cited by 524 · see citing works
The present and future of the Cancer Dependency Map
Arafeh, R., Shibue, T., Dempster, J. M., Hahn, W. C., & Vazquez, F. (2025) · Nature Reviews Cancer · doi:10.1038/s41568-024-00763-x · Cited by 454 · see citing works
CRISPR-Based Therapeutic Genome Editing: Strategies and In Vivo Delivery by AAV Vectors
Wang, D., Zhang, F., & Gao, G. (2020) · Cell · doi:10.1016/j.cell.2020.03.023 · Cited by 526 · see citing works
Comparison 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 508 · see citing works
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 510 · see citing works
Inheritable silencing of endogenous genes by hit-and-run targeted epigenetic editing
Amabile, A., Migliara, A., Capasso, P., Biffi, M., Cittaro, D., Naldini, L., & Lombardo, A. (2016) · Cell · doi:10.1016/j.cell.2016.09.006 · Cited by 516 · see citing works
Rescue of Fragile X Syndrome Neurons by DNA Methylation Editing of the FMR1 Gene
Liu, X. S., Wu, H., Krzisch, M., Wu, X., Graef, J. D., Muffat, J., Hnisz, D., Li, C. H., Yuan, B., Xu, C., et al. (2018) · Cell · doi:10.1016/j.cell.2018.01.012 · Cited by 506 · see citing works
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 491 · see citing works
Han, K., Jeng, E., Hess, G., Morgens, D., Li, A., & Bassik, M. (2017) · Nature Biotechnology · doi:10.1038/nbt.3834 · Cited by 482 · see citing works
Self-citationInduced 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 · see citing works
“…employed in loss-of-function screens, for example, to identify gene products that are required for drug resistance or to mediate viral cell death (Gilbert et al., 2014; Hart et al., 2015; Parnas et al., 2015; Shalem et al., 2014; Shi et al., 2015; Wang et al., 2015a; Wang et al., 2014a; Zhou…”
BackgroundInfluentialAn 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 472 · see citing works
Mumbach, M. R., Satpathy, A. T., Boyle, E. A., Dai, C., Gowen, B. G., Cho, S. W., Nguyen, M. L., Rubin, A. J., Granja, J. M., Kazane, K. R., et al. (2017) · Nature Genetics · doi:10.1038/ng.3963 · Cited by 490 · see citing works
Klann, T. S., Black, J. B., Chellappan, M., Safi, A., Song, L., Hilton, I. B., Crawford, G. E., Reddy, T. E., & Gersbach, C. A. (2017) · Nature Biotechnology · doi:10.1038/nbt.3853 · Cited by 447 · see citing works
Directed evolution using dCas9-targeted somatic hypermutation in mammalian cells
Hess, G. T., Frésard, L., Han, K., Lee, C. H., Li, A., Cimprich, K. A., Montgomery, S. B., & Bassik, M. C. (2016) · Nature Methods · doi:10.1038/nmeth.4038 · Cited by 469 · see citing works
Self-citationEmerging roles of lncRNA in cancer and therapeutic opportunities.
Jiang, M., Ni, J., Cui, W., Wang, B., & Zhuo, W. (2019) · PubMed Central · Cited by 476 · see citing works
Synthetic lethality as an engine for cancer drug target discovery
Huang, A., Garraway, L. A., Ashworth, A., & Weber, B. L. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0046-z · Cited by 470 · see citing works
Combinatorial single-cell CRISPR screens by direct guide RNA capture and targeted sequencing
Replogle, J. M., Norman, T. M., Xu, A., Hussmann, J. A., Chen, J., Cogan, J. Z., Meer, E. J., Terry, J. M., Riordan, D. P., Srinivas, N., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0470-y · Cited by 465 · see citing works
Self-citationIn vivo target gene activation via CRISPR/Cas9-mediated trans-epigenetic modulation
Liao, H.-K., Hatanaka, F., Araoka, T., Reddy, P., Wu, M.-Z., Sui, Y., Yamauchi, T., Sakurai, M., O’Keefe, D. D., Núñez-Delicado, E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.10.025 · Cited by 451 · see citing works
Versatile protein tagging in cells with split fluorescent protein
Kamiyama, D., Sekine, S., Barsi‐Rhyne, B., Hu, J., Chen, B., Gilbert, L. A., Ishikawa, H., Leonetti, M. D., Marshall, W. F., Weissman, J. S., et al. (2016) · Nature Communications · doi:10.1038/ncomms11046 · Cited by 450 · see citing works
Self-citationPromoter of lncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element
Cho, S. W., Xu, J., Sun, R., Mumbach, M. R., Carter, A. C., Chen, Y. G., Yost, K. E., Kim, J., He, J., Nevins, S. A., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.068 · Cited by 459 · see citing works
Self-citationAm I ready for CRISPR? A user's guide to genetic screens
Doench, J. G. (2018) · Nature Reviews Genetics · doi:10.1038/nrg.2017.97 · Cited by 452 · see citing works
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 · see citing works
A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment
Hyer, M. L., Milhollen, M. A., Ciavarri, J., Fleming, P., Traore, T., Sappal, D., Huck, J., Shi, J., Gavin, J., Brownell, J., et al. (2018) · Nature Medicine · doi:10.1038/nm.4474 · Cited by 447 · see citing works
Integrative analysis of pooled CRISPR genetic screens using MAGeCKFlute
Wang, B., Wang, M., Zhang, W., Xiao, T., Chen, C.-H., Wu, A., Wu, F., Traugh, N. C., Wang, X., Li, Z., et al. (2019) · Nature Protocols · doi:10.1038/s41596-018-0113-7 · Cited by 433 · see citing works
Cornerstones of CRISPR–Cas in drug discovery and therapy
Fellmann, C., Gowen, B. G., Lin, P., Doudna, J. A., & Corn, J. E. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.238 · Cited by 442 · see citing works
A Genome-wide CRISPR Screen in Primary Immune Cells to Dissect Regulatory Networks
Parnas, O., Jovanovic, M., Eisenhaure, T. M., Herbst, R. H., Dixit, A., Ye, C. J., Przybylski, D., Platt, R. J., Tirosh, I., Sanjana, N. E., et al. (2015) · Cell · doi:10.1016/j.cell.2015.06.059 · Cited by 440 · 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 in cancer biology and therapy
Katti, A., Diaz, B. J., Caragine, C. M., Sanjana, N. E., & Dow, L. E. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00441-w · Cited by 440 · see citing works
Zhu, S., Li, W., Liu, J., Chen, C.-H., Liao, Q., Xu, P., Xu, H., Xiao, T., Cao, Z., Peng, J., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3715 · Cited by 420 · see citing works
Elia, I., Broekaert, D., Christen, S., Boon, R., Radaelli, E., Orth, M. F., Verfaillie, C. M., Grünewald, T. G. P., & Fendt, S. (2017) · Nature Communications · doi:10.1038/ncomms15267 · Cited by 426 · 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
CRISPR knockout screening outperforms shRNA and CRISPRi in identifying essential genes
Evers, B., Jastrzebski, K., Heijmans, J. P. M., Grernrum, W., Beijersbergen, R. L., & Bernards, R. (2016) · Nature Biotechnology · doi:10.1038/nbt.3536 · Cited by 410 · see citing works
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 415 · see citing works
Self-citationExploring genetic interaction manifolds constructed from rich single-cell phenotypes
Norman, T. M., Horlbeck, M. A., Replogle, J. M., Ge, A. Y., Xu, A., Jost, M., Gilbert, L. A., & Weissman, J. S. (2019) · Science · doi:10.1126/science.aax4438 · Cited by 392 · see citing works
Self-citationGenome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis
Tian, R., Abarientos, A., Hong, J., Hashemi, S. H., Yan, R., Dräger, N., Leng, K., Nalls, M. A., Singleton, A. B., Xu, K., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00862-0 · Cited by 414 · see citing works
Self-citationThe CRISPR-Cas toolbox and gene editing technologies
Liu, G., Lin, Q., Jin, S., & Gao, C. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.12.002 · Cited by 410 · 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
Systematic comparison of CRISPR/Cas9 and RNAi screens for essential genes
Morgens, D. W., Deans, R. M., Li, A., & Bassik, M. C. (2016) · Nature Biotechnology · doi:10.1038/nbt.3567 · Cited by 384 · see citing works
Self-citationApplications of the CRISPR-Cas9 system in cancer biology
Sánchez-Rivera, F. J., & Jacks, T. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3950 · Cited by 405 · see citing works
Site-specific manipulation of Arabidopsis loci using CRISPR-Cas9 SunTag systems
Papikian, A., Liu, W., Gallego‐Bartolomé, J., & Jacobsen, S. E. (2019) · Nature Communications · doi:10.1038/s41467-019-08736-7 · Cited by 407 · see citing works
TSGene 2.0: an updated literature-based knowledgebase for tumor suppressor genes
Zhao, M., Kim, P., Mitra, R., Zhao, J., & Zhao, Z. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1268 · Cited by 400 · 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
High-Throughput Screening: today’s biochemical and cell-based approaches
Blay, V., Tolani, B., Ho, S. P., & Arkin, M. R. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.07.024 · Cited by 404 · see citing works
Anderson, D. J., Moigne, R. L., Djakovic, S. N., Kumar, B., Rice, J., Wong, S., Wang, J., Yao, B., Valle, E., Soly, S. K. V., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.10.002 · Cited by 391 · see citing works
Self-citationVariant interpretation: functional assays to the rescue
Starita, L. M., Ahituv, N., Dunham, M. J., Kitzman, J. O., Roth, F. P., Seelig, G., Shendure, J., & Fowler, D. M. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.07.014 · Cited by 381 · see citing works
Combinatorial CRISPR–Cas9 screens for de novo mapping of genetic interactions
Shen, J. P., Zhao, D., Sasik, R., Luebeck, J., Birmingham, A., Bojorquez-Gomez, A., Licon, K., Klepper, K., Pekin, D., Beckett, A. N., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4225 · Cited by 359 · see citing works
Self-citation
- Authors
- 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., Qi, L. S., Kampmann, M., & Weissman, J. S.
- Affiliations
- QB3 (US)
- University of California, San Francisco (US)
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Kampmann, Martin
- Weissman, Jonathan S.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 159
- Issue
- 3
- Pages
- 647-661
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4253859
- OpenAlex
- W2152505144
- Cited by
- 2,728
- References
- 60
- Citations by year
- 2026: 190 · 2025: 211 · 2024: 265 · 2023: 212 · 2022: 261 · 2021: 285 · 2020: 285 · 2019: 255 · 2018: 221 · 2017: 214 · 2016: 182 · 2015: 125 · 2014: 14 · 2013: 1 · 2012: 1
- FWCI
- 73.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- PMC
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (DP5OD017887, 1dp2hd084069-01)
- National Institute on Aging (P01AG010770)
- National Institute on Drug Abuse (R01DA036858)
- National Cancer Institute (K99CA181494, U01CA168370)
- National Institute of General Medical Sciences (T32GM008284, P50GM081879, R01GM100341, P50GM102706, R01GM100518)
- National Institute of Biomedical Imaging and Bioengineering (T32EB009383)
- 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 interference, CRISPR activation, transcriptional repression, transcriptional activation, gene essentiality, tumor suppressor, cholera toxin, diphtheria toxin, pathogen entry, retrotranslocation, off-target effects
- MeSH terms
- Cell Line, Cholera Toxin, Diphtheria Toxin, Genetic Techniques, Humans, Transcription, Genetic, Genome, Human, 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
