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Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex
Open accessAbstract
Systematic interrogation of gene function requires the ability to perturb gene expression in a robust and generalizable manner. Here we describe structure-guided engineering of a CRISPR-Cas9 complex to mediate efficient transcriptional activation at endogenous genomic loci. We used these engineered Cas9 activation complexes to investigate single-guide RNA (sgRNA) targeting rules for effective transcriptional activation, to demonstrate multiplexed activation of ten genes simultaneously, and to upregulate long intergenic non-coding RNA (lincRNA) transcripts. We also synthesized a library consisting of 70,290 guides targeting all human RefSeq coding isoforms to screen for genes that, upon activation, confer resistance to a BRAF inhibitor. The top hits included genes previously shown to be able to confer resistance, and novel candidates were validated using individual sgRNA and complementary DNA overexpression. A gene expression signature based on the top screening hits correlated with markers of BRAF inhibitor resistance in cell lines and patient-derived samples. These results collectively demonstrate the potential of Cas9-based activators as a powerful genetic perturbation technology.
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“Because of the relatively large size of 4277 bp of dCas9-VPR cDNA, the authors used a dual rAAV system to express the dCas9-VPR and gRNA expression cassettes [223,224].”
From Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays (2020) · cites this paper as [224]
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“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 [30]
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“Novel strategies of Cas9-based transcription modulators rapidly appeared prompted by the fusion of dCas9 or gRNA to different activator or repressor elements, with multiple degrees of modulation and specificity, and enabling single or multiplexed transcriptional control [74,75,76].”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [74]
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“This dCas9-effector strategy has already been applied in genome wide screening study in which gain-of-function mutations in melanoma cells that confer drug resistance were identified.46”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [46]
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“…of Genome-wide CRISPR Analyses to Reveal Disease-Contributing Genes and Pathways Recent development of CRISPR-based genome editing has enabled pooled genome-wide screens in mammalian cells (Gilbert et al., 2014; Konermann et al., 2015; Parnas et al., 2015; Shalem et al., 2014; Wang et al., 2014).”
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“…et al. 2013a; Gao et al. 2014), next generation dCas9-based activator platforms are under development with more robust activity (Chakraborty et al. 2014; Gao et al. 2014; Gilbert et al. 2014; Kabadi et al. 2014; Tanenbaum et al. 2014; Chavez et al. 2015; Hilton et al. 2015; Konermann et al. 2015).”
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“For instance, though several studies have reported correlation between the relative expression level and the proximity of the gRNA position to TSS [23, 30], this correlation is not evident when assessing our full library of tested scRNAs primarily targeting dcas9 to the TSS-200 to TSS+1 window (Fig.”
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“…activators (VP64, a synthetic tetramer of the Herpes Simplex Viral Protein or p65 a transcription factor activation domain) or transcriptional repressors [KRAB, a Kruppel-associated box and the transcriptional repressor of Kox1, or 4X mSin Interaction Domain (SID; Konermann et al., 2015)].”
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“For each TALE-TF, the TALE repeats were cloned into an rAAV transfer plasmid using a PCR-based, Golden Gate cloning strategy as previously described (Konermann et al., 2015; Sanjana et al., 2012; Tarazona et al., 2011).”
MethodApplications of CRISPR-Cas Enzymes in Cancer Therapeutics and Detection
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Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity
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Harnessing CRISPR/Cas systems for programmable transcriptional and post-transcriptional regulation
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“The CRISPR/dCas9 system has been used to create highly efficient, programmable, genome-wide scale transcriptional regulators (Gilbert et al., 2014; Gilbert et al., 2013; Konermann et al., 2015).”
MethodlncExACT1 and DCHS2 Regulate Physiological and Pathological Cardiac Growth
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Epigenome editing technologies for discovery and medicine
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“Examples include the tripartite activator VPR 36 (VP64, p65 and Rta) as well as peptide-or RNA-based recruitment systems like SunTag 37 , synergistic activation mediator (SAM) 38 and CRISPR-DREAM 39 .”
CRISPR/Cas9-mediated noncoding RNA editing in human cancers
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“Four aptamers, MS2 (23), PP7 (24), BoxB (25) and com (26), have been used in sgRNAs for target-binding purposes (22,27–29).”
Human thermogenic adipocyte regulation by the long noncoding RNA LINC00473
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A new age in functional genomics using CRISPR/Cas9 in arrayed library screening
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“Konermann et al. (2015) designed a “Synergistic Activation Mediator” system consisting of dCas9 linked to VP64 (a fusion of four copies of the transcriptional activator VP16), in addition to a separate fusion protein of two distinct classes of activation domains (p65 and HSF1) linked to the…”
BackgroundCRISPR Modeling and Correction of Cardiovascular Disease
Liu, N., & Olson, E. N. (2022) · Circulation Research · doi:10.1161/circresaha.122.320496 · Cited by 120
Epigenetic gene regulation in plants and its potential applications in crop improvement
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“The MS2 system uses the high-affinity interaction between the viral coat protein MS2 and its aptamer ligand 290,291 , which can be fused to the sgRNA in multiple copies.”
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“Recently, transcriptional activation with CRISPRCas9 [Konermann et al., 2015] and TAL effectors [Zhang et al., 2011] emerged as an efficient alternative to ZFPs.”
BackgroundEngineering of temperature- and light-switchable Cas9 variants
Richter, F. M., Fonfara, I., Bouazza‐Arostegui, B., Schumacher, C. H., Bratovič, M., Charpentier, E., & Möglich, A. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkw930 · Cited by 114
“tsRC9 could also be applied to transcriptional regulation in eukaryotic cells (14), provided that the system under study can withstand prolonged periods at ∼30◦C.”
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Zinc Fingers, TALEs, and CRISPR Systems: A Comparison of Tools for Epigenome Editing
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Advances in promoter engineering: Novel applications and predefined transcriptional control
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CRISPR/Cas9-mediated genome engineering of CHO cell factories: application and perspectives
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“Thus CRISPR/Cas9 screens have recently been applied to identify genes responsible for cancer drug resistance [65, 69] and mechanisms underlying toxin activity [68, 70].”
BackgroundPrecision cancer mouse models through genome editing with CRISPR-Cas9
Mou, H., Kennedy, Z., Anderson, D. G., Yin, H., & Xue, W. (2015) · Genome Medicine · doi:10.1186/s13073-015-0178-7 · Cited by 116
“domains [89–94] and chimerical sgRNA scaffold [95,96] can be”
BackgroundNon-Viral Delivery To Enable Genome Editing
Rui, Y., Wilson, D. R., & Green, J. J. (2018) · Trends in biotechnology · doi:10.1016/j.tibtech.2018.08.010 · Cited by 115
“The DNA binding capabilities of these genome editing enzymes have been further harnessed to enable site-specific single base pair editing [9, 10] and epigenetic [11, 12] or transcriptional [13, 14] modulation of gene expression.”
BackgroundEngineering cell sensing and responses using a GPCR-coupled CRISPR-Cas system
Kipniss, N. H., Dingal, P. C. D. P., Abbott, T. R., Gao, Y., Wang, H., Dominguez, A. A., Labanieh, L., & Qi, L. S. (2017) · Nature Communications · doi:10.1038/s41467-017-02075-1 · Cited by 113
“The fitted dose response curve based on the Hill Equation revealed the effective CNO concentration to achieve half-maximal GFP level (EC50) at 105 ± 4 nM (R2 = 0.95, Fig.”
BackgroundInfluentialCurrent and future prospects for CRISPR‐based tools in bacteria
Luo, M. L., Leenay, R. T., & Beisel, C. L. (2015) · Biotechnology and Bioengineering · doi:10.1002/bit.25851 · Cited by 116
“…was transitioning from single-domain fusions, such as between dCas9 and the VP64 activating domain or the KRAB repressing domain, to extensions of dCas9 or the sgRNA that recruit the regulatory domains (Konermann et al., 2014; Shechner et al., 2015; Tanenbaum et al., 2014; Zalatan et al., 2014).”
BackgroundLncRNA AK023948 is a positive regulator of AKT
Koirala, P., Huang, J., Ho, T.-T., Wu, F., Ding, X., & Mo, Y. (2017) · Nature Communications · doi:10.1038/ncomms14422 · Cited by 114
“2A) including AK023948 were upregulated presumably because of function of the corresponding SAM gRNAs.”
InfluentialCarleton, J. B., Berrett, K. C., & Gertz, J. (2017) · Cell Systems · doi:10.1016/j.cels.2017.08.011 · Cited by 113
“While the dCas9-SID fusion has been targeted to an enhancer (Konermann et al., 2015), it has yet to be employed in blocking a transcriptional response.”
Shen, M., Wang, F., Li, M., Sah, N., Stockton, M. E., Tidei, J. J., Gao, Y., Korabelnikov, T., Kannan, S., Vevea, J., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0338-y · Cited by 111
Cell-specific CRISPR–Cas9 activation by microRNA-dependent expression of anti-CRISPR proteins
Hoffmann, M. D., Aschenbrenner, S., Große, S., Rapti, K., Domenger, C., Fakhiri, J., Mastel, M., Börner, K., Eils, R., Grimm, D., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz271 · Cited by 112
Sherkatghanad, Z., Abdar, M., Charlier, J., & Makarenkov, V. (2023) · Briefings in Bioinformatics · doi:10.1093/bib/bbad131 · Cited by 123
“position-specific Shalem [105], edu/SSC features Zhou [106] Gilbert [107] Konermann [108]”
BackgroundInfluentialCRISPR guide RNA design for research applications
Mohr, S. E., Hu, Y., Ewen‐Campen, B., Housden, B. E., Viswanatha, R., & Perrimon, N. (2016) · FEBS Journal · doi:10.1111/febs.13777 · Cited by 112
Editing the genome of hiPSC with CRISPR/Cas9: disease models
Bassett, A. R. (2017) · Mammalian Genome · doi:10.1007/s00335-017-9684-9 · Cited by 125
The CRISPR /Cas revolution reaches the RNA world: Cas13, a new Swiss Army knife for plant biologists
Wolter, F., & Puchta, H. (2018) · The Plant Journal · doi:10.1111/tpj.13899 · Cited by 113
“By fusing this nuclease ‘dead’ Cas9 (dCas9) directly or indirectly to an effector domain, it can then be used to guide diverse enzymatic functions to any specific site in the genome (Gilbert et al., 2013; Konermann et al., 2015).”
BackgroundPrediction of CRISPR sgRNA Activity Using a Deep Convolutional Neural Network
Xue, L., Tang, B., Chen, W., & Luo, J. (2018) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.8b00368 · Cited by 113
CRISPR/Cas brings plant biology and breeding into the fast lane
Schindele, A., Dorn, A., & Puchta, H. (2019) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2019.08.006 · Cited by 115
“Indirect fusions are mediated through modified sgRNAs, where small RNA aptamers act as a scaffold for RNA binding proteins [17].”
BackgroundVelazquez, J. J., LeGraw, R., Moghadam, F., Tan, Y., Kilbourne, J. A., Maggiore, J. C., Hislop, J., Liu, S., Cats, D., Lopes, S. M. C. D. S., et al. (2020) · Cell Systems · doi:10.1016/j.cels.2020.11.002 · Cited by 103
“To confine CYP3A4 activation to hepatocytes, we used a version of CRISPRa in which dCas9 is driven by an AAT promoter (pAAT) and two engineered hairpin aptamers in the gRNA recruit an MS2 bacteriophage coat protein (MCP)-fused transcriptional activation complex (Konermann et al., 2015) (Figures S1Q and S1R).”
MethodCRISPR-mediated Activation of Latent HIV-1 Expression
Limsirichai, P., Gaj, T., & Schaffer, D. V. (2015) · Molecular Therapy · doi:10.1038/mt.2015.213 · Cited by 112
Selma, S., Bernabé‐Orts, J. M., Vázquez‐Vilar, M., Diego‐Martin, B., Ajenjo-Bauza, M., García‐Carpintero, V., Granell, A., & Orzáez, D. (2019) · Plant Biotechnology Journal · doi:10.1111/pbi.13138 · Cited by 109
Pramanik, D., Shelake, R. M., Kim, M. J., & Kim, J. (2020) · Molecular Plant · doi:10.1016/j.molp.2020.11.002 · Cited by 110
Metabolic engineering of plant secondary metabolites: prospects and its technological challenges
Devi, A. M., Devi, K. K., Pukhrambam, P. D., Devi, M. L., & Das, S. (2023) · Frontiers in Plant Science · doi:10.3389/fpls.2023.1171154 · Cited by 128
“In the second generation, multiplexed gene activation of up to 10 genes, using 10sgRNAs was achieved using the synergistic activation mediator system (SAMS) (Konermann et al., 2015).”
MethodGenome editing: the road of CRISPR/Cas9 from bench to clinic
Eid, A., & Mahfouz, M. M. (2016) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.111 · Cited by 111
CRISPR/Cas9 library screening for drug target discovery
Kurata, M., Yamamoto, K., Moriarity, B. S., Kitagawa, M., & Largaespada, D. A. (2017) · Journal of Human Genetics · doi:10.1038/s10038-017-0376-9 · Cited by 108
“Human CRISPR Activation Library (SAM library) Activation Positive Vemurafenib A375 EGFR, PCDH7, ITGB5, ARHGFE1, BCAR3, GPR35, TFAP2C [7]”
Strategies to Increase On-Target and Reduce Off-Target Effects of the CRISPR/Cas9 System in Plants
Hajiahmadi, Z., Movahedi, A., Wei, H., Li, D., Orooji, Y., Ruan, H., & Zhuge, Q. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20153719 · Cited by 112
“(2015), the tetraloop and stem-loop II of the sgRNA can tolerate aptamer addition with no effect on the sgRNA activity [117].”
BackgroundMatsa, E., Ahrens, J. H., & Wu, J. C. (2016) · Physiological Reviews · doi:10.1152/physrev.00036.2015 · Cited by 105
“Notably, some groups have synthesized CRISPR/Cas9 libraries consisting of 70,290 guides targeting all human RefSeq coding isoforms (138), demonstrating that this technology constitutes a powerful genetic perturbation tool, with wide applications in precision medicine.”
BackgroundStrategies to Annotate and Characterize Long Noncoding RNAs: Advantages and Pitfalls
Cao, H., Wahlestedt, C., & Kapranov, P. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.06.002 · Cited by 105
CRISPR-based tools for targeted transcriptional and epigenetic regulation in plants
Lee, J. E., Neumann, M., Duro, D. I., & Schmid, M. (2019) · PLoS ONE · doi:10.1371/journal.pone.0222778 · Cited by 110
A lncRNA-SWI/SNF complex crosstalk controls transcriptional activation at specific promoter regions
Grossi, E., Raimondi, I., Goñi, E., González, J., Marchese, F. P., Chapaprieta, V., Martín-Subero, J. I., Guo, S., & Huarte, M. (2020) · Nature Communications · doi:10.1038/s41467-020-14623-3 · Cited by 112
Applications of CRISPR/Cas9 in the Synthesis of Secondary Metabolites in Filamentous Fungi
Jiang, C., Lv, G., Tu, Y., Cheng, X., Duan, Y., Zeng, B., & He, B. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.638096 · Cited by 111
“CRISPR activation (CRISPRa), can be achieved through direct fusing dCas9 with activation domains, such as VP64/p65/HSF1 (Bikard et al., 2013; Gilbert et al., 2014; Konermann et al., 2015; Jia et al., 2018; Strezoska et al., 2020).”
BackgrounddCas9: A Versatile Tool for Epigenome Editing
Brocken, D. J. W., Tark‐Dame, M., & Dame, R. T. (2017) · Current Issues in Molecular Biology · doi:10.21775/cimb.026.015 · Cited by 113
“The application of dCas9 in forward screening using targeted transcription factors (TTFs) was shown to permit highly specific genome-scale transcription modulation (Gilbert et al., 2014; Konermann et al., 2015).”
BackgroundMethodInfluentialZha, H., Wang, X., Zhu, Y. J., Chen, D., Han, X., Yang, F., Gao, J., Hu, C., Shu, C., Feng, Y., et al. (2018) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-18-0272 · Cited by 115
“We applied SAM technology to activate C3 expression in B16F10 cells (37) and validated the expression of C3 in the B16-C3 cell supernatant by C3 ELISA (Fig.”
MethodCRISPR-based therapeutics: current challenges and future applications
Modell, A. E., Lim, D., Nguyen, T. M., Sreekanth, V., & Choudhary, A. (2021) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2021.10.012 · Cited by 114
Ligand-binding domains of nuclear receptors facilitate tight control of split CRISPR activity
Nguyen, D., Miyaoka, Y., Gilbert, L. A., Mayerl, S. J., Lee, B. H., Weissman, J. S., Conklin, B. R., & Wells, J. A. (2016) · Nature Communications · doi:10.1038/ncomms12009 · Cited by 107
Chen, F., Li, X., Aquadro, E., Haigh, S. B., Zhou, J., Stepp, D. W., Weintraub, N. L., Barman, S. A., & Fulton, D. J. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.08.003 · Cited by 105
“The ability of CRISPR-ON to drive Nox1/Nox2/Nox4/Nox5 gene transcription as well as ROS production was attenuated in the presence of scriptaid (Fig.”
BackgroundInfluentialWang, G., Chow, R. D.-W., Ye, L., Guzman, C. D., Dai, X., Dong, M. B., Zhang, F., Sharp, P. A., Platt, R. J., & Chen, S. (2018) · Science Advances · doi:10.1126/sciadv.aao5508 · Cited by 101
Self-citationFontana, J. T., Dong, C., Kiattisewee, C., Chavali, V. P., Tickman, B. I., Carothers, J. M., & Zalatan, J. G. (2020) · Nature Communications · doi:10.1038/s41467-020-15454-y · Cited by 108
Proximity labeling identifies a repertoire of site-specific R-loop modulators
Yan, Q., Wulfridge, P., Doherty, J. K., Fernández-Luna, J. L., Real, P. J., Tang, H., & Sarma, K. (2022) · Nature Communications · doi:10.1038/s41467-021-27722-6 · Cited by 106
Modeling Disease In Vivo With CRISPR/Cas9
Dow, L. E. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.07.006 · Cited by 111
“In addition, nuclease-inactive ‘dead’ Cas9 (dCas9) has been adapted to enable suppression of gene transcription (CRISPRi) or activation of endogenous gene expression (CRISPRa) [87–92].”
Resources for the design of CRISPR gene editing experiments
Graham, D. B., & Root, D. E. (2015) · Genome biology · doi:10.1186/s13059-015-0823-x · Cited by 108
“Few such screens have been published to date, and these systems are not reviewed here, but given the advantages of modulating the endogenous gene in context versus expressing the CDS from an artificial promoter, CRISPR transcriptional modifications promise to be a popular screening approach [13, 22, 24, 26].”
BackgroundInfluentialCRISPR technologies for stem cell engineering and regenerative medicine
Hsu, M., Chang, Y., Truong, V. A., Lai, P., Nguyen, T. K. N., & Hu, Y. (2019) · Biotechnology Advances · doi:10.1016/j.biotechadv.2019.107447 · Cited by 106
Photoswitchable gRNAs for Spatiotemporally Controlled CRISPR-Cas-Based Genomic Regulation
Moroz, E., Satyapertiwi, D., Ramel, M., Høgset, H., Sunyovszki, I., Liu, Z., Wojciechowski, J. P., Zhang, Y., Grigsby, C. L., Brito, L., et al. (2020) · ACS Central Science · doi:10.1021/acscentsci.9b01093 · Cited by 104
Destabilizing heterochromatin by APOE mediates senescence
Zhao, H., Ji, Q., Wu, Z., Wang, S., Ren, J., Yan, K., Wang, Z., Hu, J., Chu, Q., Hu, H., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00186-z · Cited by 104
Kong, X., Zhang, H., Li, G., Wang, Z., Kong, X., Wang, L., Xue, M., Zhang, W., Wang, Y., Lin, J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37829-7 · Cited by 110
“It is also plausible that the hypercompact size of enOsCas12f1 (433 aa) and enRhCas12f1 (415 aa) could potentially enable their use in derivative genome engineering applications, including base editing, prime editing, retron editing, epigenome editing, and gene expression regulation 8,10 – 12 , 41 .”
Enabling functional genomics with genome engineeringPreprint
Hilton, I. B., & Gersbach, C. A. (2015) · Genome Research · doi:10.1101/gr.190124.115 · Cited by 106
“In addition, nuclease-inactivated dCas9-based repressors and activators can be used in loss-offunction and gain-of-function screens, respectively (Gilbert et al. 2014; Konermann et al. 2015).”
BackgroundMethodCRISPR/Cas9 for Human Genome Engineering and Disease Research
Xiong, X., Chen, M., Lim, W. A., Zhao, D., & Qi, L. S. (2016) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-083115-022258 · Cited by 111
Emerging roles for long noncoding RNAs in skeletal biology and disease
Huynh, N. P. T., Anderson, B. A., Guilak, F., & McAlinden, A. (2016) · Connective Tissue Research · doi:10.1080/03008207.2016.1194406 · Cited by 105
“This includes, but not limited to, dCas9-KRAB (253,254) for gene repression and dCas9-VP48 (255), dCas9-VP64 (256) (257), dCas9-p300 (258), dCas9-VP64/p65 (259) for gene activation.”
Background
Metadata
- Authors
- 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., Nureki, O., & Zhang, F.
- Affiliations
- Broad Institute (US)
- The University of Tokyo (JP)
- Corresponding author
- Zhang, Feng
- ORCID
- Venue
- Nature
- Published
- 2014-12-10
- Volume
- 517
- Issue
- 7536
- Pages
- 583-588
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4420636
- OpenAlex
- W2127862779
- Cited by
- 2,825
- References
- 52
- Citations by year
- 2026: 154 · 2025: 204 · 2024: 266 · 2023: 236 · 2022: 279 · 2021: 281 · 2020: 301 · 2019: 270 · 2018: 261 · 2017: 229 · 2016: 214 · 2015: 122 · 2014: 3
- FWCI
- 77.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- PMC
- Funders
- Japan Society for the Promotion of Science (26291010)
- National Institute of Mental Health (DP1MH100706)
- National Institute of Neurological Disorders and Stroke (R01NS062849, 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 regulation and disease
- Keywords
- CRISPR/Cas9, transcriptional activation, long intergenic non-coding RNA, gain-of-function screen, BRAF inhibitor resistance, melanoma, drug resistance, gene expression signatures, gene perturbation
- MeSH terms
- Genetic Engineering, Genetic Testing, Humans, Indoles, Melanoma, Sulfonamides, Reproducibility of Results, Transcriptional Activation, Gene Library, Up-Regulation, Genome, Human, Gene Expression Regulation, Neoplastic, DNA, Complementary, Drug Resistance, Neoplasm, RNA, Untranslated, Cell Line, Tumor, Proto-Oncogene Proteins B-raf, Genetic Loci, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas Systems, CRISPR-Associated Proteins
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