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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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Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome
Li, B., & Dewey, C. N. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-323 · Cited by 22,179
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
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
Barretina, J., Caponigro, G., Stransky, N., Venkatesan, K., Margolin, A. A., Kim, S., Wilson, C. J., Lehár, J., Kryukov, G. V., Sonkin, D., et al. (2012) · Nature · doi:10.1038/nature11003 · Cited by 7,950
Molecular signatures database (MSigDB) 3.0
Liberzon, A., Subramanian, A., Pinchback, R., Thorvaldsdóttir, H., Tamayo, P., & Mesirov, J. P. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr260 · Cited by 7,111
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-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-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
Self-citationSystematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1
Barbie, D. A., Tamayo, P., Boehm, J. S., Kim, S. Y., Moody, S. E., Dunn, I. F., Schinzel, A. C., Sandy, P., Meylan, E., Scholl, C., et al. (2009) · Nature · doi:10.1038/nature08460 · Cited by 3,922
Integrins in cancer: biological implications and therapeutic opportunities
Desgrosellier, J. S., & Cheresh, D. A. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2748 · Cited by 3,815
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CRISPR–Cas-mediated transcriptional control and epi-mutagenesis
Gardiner, J., Ghoshal, B., Wang, M., & Jacobsen, S. E. (2022) · PLANT PHYSIOLOGY · doi:10.1093/plphys/kiac033 · Cited by 46
“even more or different effector proteins to a target site via effector protein interactions with both the gRNA and the dCas9 (Konermann et al., 2015; Lowder et al., 2018; Pan et al., 2021) (Figure 2E).”
InfluentialMACC1 promotes pancreatic cancer metastasis by interacting with the EMT regulator SNAI1
Zhang, X., Luo, Y., Cen, Y., Qiu, X., Li, J., Jie, M., Yang, S., & Qin, S. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05285-8 · Cited by 46
“To obtain stable cell lines expressing cDNA for FN1, a CRISPRmediated activation system was used for transcriptional activation of FN1, the virus package and the infection method, as previously described [49, 50].”
MethodDevelopment of delivery strategies for CRISPR‐Cas9 genome editing
Liu, Q., Yang, J., Xing, Y., Zhao, Y., & Liu, Y. (2023) · BMEMat · doi:10.1002/bmm2.12025 · Cited by 47
Dual-role transcription factors stabilize intermediate expression levels
He, J., Huo, X., Pei, G., Jia, Z., Yan, Y., Yu, J., Qu, H., Xie, Y., Yuan, J., Zheng, Y., et al. (2024) · Cell · doi:10.1016/j.cell.2024.03.023 · Cited by 46
Bidirectional epigenetic editing reveals hierarchies in gene regulation
Pacalin, N. M., Steinhart, Z., Shi, Q., Belk, J. A., Dorovskyi, D., Kraft, K., Parker, K. R., Shy, B. R., Marson, A., & Chang, H. Y. (2024) · Nature Biotechnology · doi:10.1038/s41587-024-02213-3 · Cited by 48
“Programmable epigenetic editing tools, specifically CRISPR activation (CRISPRa) 1–5 and CRISPR interference (CRISPRi) 6,7 , are valuable for uncovering functional effects of genes and non-coding genetic elements, such as enhancers 8–15 .”
Haimovich, A. D., Muir, P., & Isaacs, F. J. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3956 · Cited by 48
Schmieder, V., Bydlinski, N., Strasser, R., Baumann, M., Kildegaard, H. F., Jadhav, V., & Borth, N. (2017) · Biotechnology Journal · doi:10.1002/biot.201700211 · Cited by 46
CRISPR/Cas9: the Jedi against the dark empire of diseases
Khan, S., Mahmood, M. S., Rahman, S. U., Zafar, H., Khan, S. H., khan, Z., & Ahmad, A. (2018) · Journal of Biomedical Science · doi:10.1186/s12929-018-0425-5 · Cited by 49
Transcription-associated histone pruning demarcates macroH2A chromatin domains
Sun, Z., Filipescu, D., Andrade, J., Gaspar‐Maia, A., Ueberheide, B. M., & Bernstein, E. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0134-5 · Cited by 48
Lau, C., Ho, J. W., Lo, P. K., & Tin, C. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.04.015 · Cited by 46
Microbial CRISPRi and CRISPRa Systems for Metabolic Engineering
Zheng, Y., Su, T., & Qi, Q. (2019) · Biotechnology and Bioprocess Engineering · doi:10.1007/s12257-019-0107-5 · Cited by 46
Wang, K., Gong, Q., & Ye, X. (2019) · Theoretical and Applied Genetics · doi:10.1007/s00122-019-03464-4 · Cited by 49
Monitoring the Levels of Cellular NF-κB Activation States
Meier‐Soelch, J., Mayr‐Buro, C., Juli, J. U., Leib, L., Linne, U., Dreute, J., Papantonis, A., Schmitz, M. L., & Kracht, M. (2021) · Cancers · doi:10.3390/cancers13215351 · Cited by 53
“The CRISPR-Cas9 toolbox now enables the establishment of methods that allow monitoring functions of endogenous NF-κB in intact cells including sophisticated CRISPR-dCas9 activation systems [62,122].”
MethodCRISPR based therapeutics: a new paradigm in cancer precision medicine
Das, S., Bano, S., Kapse, P., & Kundu, G. C. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01552-6 · Cited by 47
Recent advancements in CRISPR/Cas technology for accelerated crop improvement
Das, D., Singha, D. L., Paswan, R. R., Chowdhury, N., Sharma, M., Reddy, P. S., & Chikkaputtaiah, C. (2022) · Planta · doi:10.1007/s00425-022-03894-3 · Cited by 50
Comparative analysis of dCas9-VP64 variants and multiplexed guide RNAs mediating CRISPR activation
Omachi, K., & Miner, J. H. (2022) · PLoS ONE · doi:10.1371/journal.pone.0270008 · Cited by 48
“protein tagging systems called SunTag (dCas9-SunTag-VP64) [10] and MS2-MCP (dCas9-VP64 + MCP-VP64) [11] were developed to increase the number of VP64s at the same locus and enhance activation efficiency.”
BackgroundMethodInfluentialYu, X., Li, S., Feng, H., Liao, X., Xing, X., Bai, Z., Liu, X., & Zhang, C. (2022) · Metabolic Engineering · doi:10.1016/j.ymben.2022.12.004 · Cited by 44
The trans-regulatory landscape of gene networks in plants
Hummel, N. F. C., Zhou, A., Li, B., Markel, K., Ornelas, I. J., & Shih, P. M. (2023) · Cell Systems · doi:10.1016/j.cels.2023.05.002 · Cited by 45
Hu, Z., Ling, S., Duan, J., Yu, Z., Che, Y., Wang, S., Zhang, S., Zhang, X., & Li, Z. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf017 · Cited by 46
“Here, we first attempted to introduce a hairpin aptamer at the “UCUU” site of the gRNA to investigate its impact on Cas12a activity, employing the MS2 aptamer, which can bind to the MS2 bacteriophage coat protein [ 32 ].”
Potential impact of genome editing in world agriculture
Martínez-Fortún, J., Phillips, D. W., & Jones, H. D. (2017) · Emerging Topics in Life Sciences · doi:10.1042/etls20170010 · Cited by 46
Engineering mammalian cells for disease diagnosis and treatment
Teixeira, A. P., & Fussenegger, M. (2018) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2018.08.008 · Cited by 45
Improvements of TKC Technology Accelerate Isolation of Transgene-Free CRISPR/Cas9-Edited Rice Plants
He, Y., Min, Z., Lihao, W., Wu, J., Wang, Q., Wang, R., & Zhao, Y. (2019) · Rice Science · doi:10.1016/j.rsci.2018.11.001 · Cited by 46
Technologies and Computational Analysis Strategies for CRISPR Applications
Clement, K., Hsu, J. Y., Canver, M. C., Joung, J. K., & Pinello, L. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.06.012 · Cited by 45
Self-citationDisruption of nuclear envelope integrity as a possible initiating event in tauopathies
Prissette, M., Fury, W., Koss, M., Racioppi, C., Fedorova, D., Dragileva, E., Clarke, G., Pohl, T., Dugan, J., Ahrens, D., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111249 · Cited by 41
Cai, J., Chen, J., Wu, T., Cheng, Z., Tian, Y., Pu, C., Shi, W., Suo, X., Wu, X., & Zhang, K. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.04.040 · Cited by 44
HIV-based lentiviral vectors: Origin and sequence differences
Johnson, N. M., Alvarado, A. F., Moffatt, T. N., Edavettal, J. M., Swaminathan, T. A., & Braun, S. E. (2021) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2021.03.018 · Cited by 45
Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes
McAllan, L., Baranas̆ić, D., Villicaña, S., Brown, S., Zhang, W., Lehne, B. C., Adamo, M., Jenkinson, A. D., Elkalaawy, M., Mohammadi, B., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38439-z · Cited by 48
Ravichandran, M., & Maddalo, D. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1273994 · Cited by 47
“For instance, CRISPRa screening in a V600E melanoma cell line treated with BRAF inhibitors revealed previously-known as well as novel gene components that confer resistance to the inhibitor (Konermann et al., 2015).”
BackgroundExosome-mediated delivery of CRISPR-Cas9: A revolutionary approach to cancer gene editing
Balaraman, A. K., Babu, M. A., Moglad, E. H. O., Mandaliya, V. B., Rekha, M. M., Gupta, S., Prasad, G. V. S., Kumari, M., Chauhan, A. S., Ali, H., et al. (2024) · Pathology - Research and Practice · doi:10.1016/j.prp.2024.155785 · Cited by 50
Yeddula, N., Xia, Y., Ke, E., Beumer, J., & Verma, I. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520110112 · Cited by 43
“The CRISPR/mutant cas9 system was used to achieve endogenous transcriptional activation of EfnA1 as reported (62).”
Method“It has been shown that the dCas9 activation complexes, with a sgRNA library, can activate multiple genes simultaneously, upregulate long non-coding RNA transcripts and identify genes conferring resistance to a BRAF inhibitor in melanoma (Konermann et al., 2015).”
BackgroundCRISPRlnc: a manually curated database of validated sgRNAs for lncRNAs
Chen, W., Zhang, G., Li, J., Zhang, X., Huang, S., Xiang, S., Hu, X., & Liu, C. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky904 · Cited by 44
“After inactivating the nuclease domain to create a dead Cas9 (dCas9) (21), accessional function elements could conduce to branching out the applications of CRISPR/Cas9 system, such as transcriptional activation (CRISPRa) (22), transcriptional interference (CRISPRi) (23,24), gene editing (CRISPRedit) (25) and so on.”
BackgroundNoorani, I. (2019) · Cancers · doi:10.3390/cancers11091335 · Cited by 45
Reversing Post-Infectious Epigenetic-Mediated Immune Suppression
Abhimanyu, A., Ontiveros, C. O., Guerra-Resendez, R. S., Nishiguchi, T., Ladki, M., Hilton, I. B., Schlesinger, L. S., & DiNardo, A. R. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.688132 · Cited by 46
Reprogramming astrocytes to motor neurons by activation of endogenous Ngn2 and Isl1
Zhou, M., Tao, X., Sui, M., Cui, M., Liu, D., Wang, B., Wang, T., Zheng, Y., Luo, J., Mu, Y., et al. (2021) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.05.020 · Cited by 44
“Dead Cas9 (dCas9), an inactivated form of Cas9, has been designed to fuse with transactivation factor to form programmable synthetic TFs, known as the CRISPR activation (CRISPRa) system (Konermann et al., 2015; Zalatan et al., 2015).”
BackgroundMethodDelivery of CRISPR-Cas9 system for screening and editing RNA binding proteins in cancer
Yan, J., Kang, D. D., Turnbull, G., & Dong, Y. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114042 · Cited by 45
Garcia‐Perez, E., Diego‐Martin, B., Quijano‐Rubio, A., Giménez, E. M., Selma, S., Orzáez, D., & Vázquez‐Vilar, M. (2022) · BMC Biotechnology · doi:10.1186/s12896-022-00741-x · Cited by 44
“Discussion CRISPR-based PTAs are becoming extensively used for endogenous genes activation in plants due to their high specificity and their effectiveness in boosting transcriptional activation [14, 33] [42].”
BackgroundCustom‐made design of metabolite composition in N. benthamiana leaves using CRISPR activators
Selma, S., Sanmartín, N., Espinosa‐Ruíz, A., Gianoglio, S., López-Gresa, M. P., Vázquez‐Vilar, M., Flors, V., Granell, A., & Orzáez, D. (2022) · Plant Biotechnology Journal · doi:10.1111/pbi.13834 · Cited by 44
“This PTA is based on the CRISPR-scRNA strategy (Konermann et al., 2015; Zalatan et al., 2015) and comprises two gene modules, a constant module with two constitutively expressed transcriptional units (TUs), and a variable module carrying the gene-specific activation programme.”
MethodRichter, F. M., Fonfara, I., Gelfert, R., Nack, J., Charpentier, E., & Möglich, A. (2017) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2017.03.025 · Cited by 44
CRISPR Screens in Synthetic Lethality and Combinatorial Therapies for Cancer
Castells‐Roca, L., Tejero, E., Rodríguez‐Santiago, B., & Surrallés, J. (2021) · Cancers · doi:10.3390/cancers13071591 · Cited by 45
“Several days of culture are necessary for the sgRNA-Cas9 duplex to alter the genome, cells must be kept in antibiotic selection to screen during 7 to 14 days [14,15,30,38], to generate KO genes; and for transcriptional upregulation via SAM complex only 4 days [30].”
CRISPR-Cas System: The Current and Emerging Translational Landscape
Bhokisham, N., Laudermilch, E., Traeger, L. L., Bonilla, T. D., Ruíz-Estévez, M., & Becker, J. R. (2023) · Cells · doi:10.3390/cells12081103 · Cited by 46
Fusion guide RNAs for orthogonal gene manipulation with Cas9 and Cpf1
Kweon, J., Jang, A.-H., Kim, D., Yang, J. W., Yoon, M.-J., Shin, H. R., Kim, J., & Kim, Y. (2017) · Nature Communications · doi:10.1038/s41467-017-01650-w · Cited by 43
An automated microfluidic gene-editing platform for deciphering cancer genes
Sinha, H., Quach, A. B. V., Vo, P. Q. N., & Shih, S. C. C. (2018) · Lab on a Chip · doi:10.1039/c8lc00470f · Cited by 44
Zfp281 Shapes the Transcriptome of Trophoblast Stem Cells and Is Essential for Placental Development
Ishiuchi, T., Ohishi, H., Sato, T., Kamimura, S., Yorino, M., Abe, S., Suzuki, A., Wakayama, T., Suyama, M., & Sasaki, H. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.028 · Cited by 43
Rewiring of endogenous signaling pathways to genomic targets for therapeutic cell reprogramming
Krawczyk, K., Scheller, L., Kim, H., & Fussenegger, M. (2020) · Nature Communications · doi:10.1038/s41467-020-14397-8 · Cited by 43
Ankley, L. M., Thomas, S. M., & Olive, A. J. (2020) · Infection and Immunity · doi:10.1128/iai.00916-19 · Cited by 44
“Two such systems, the synergistic activator mediator (SAM) and the Calabrese system, robustly induce genes in an sgRNA-dependent manner independently of their normal expression patterns (110, 113).”
BackgroundAn MXD1-derived repressor peptide identifies noncoding mediators of MYC-driven cell proliferation
Raffeiner, P., Hart, J. R., García-Caballero, D., Bar‐Peled, L., Weinberg, M. S., & Vogt, P. K. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1921786117 · Cited by 43
“The MS2 coat protein (MCP) binds with high selectivity and high affinity to the MS2 RNA aptamer (48), and MCP fused to transcriptional activator domains have been shown to effectively up-regulate gene expression (28, 47).”
BackgroundMethodInfluentialMultilayer Genetic Circuits for Dynamic Regulation of Metabolic Pathways
Cui, S., Lv, X., Xu, X., Chen, T., Zhang, H., Liu, Y., Li, J., Du, G., Ledesma‐Amaro, R., & Liu, L. (2021) · ACS Synthetic Biology · doi:10.1021/acssynbio.1c00073 · Cited by 42
Bi, S., Jiang, X., Ji, Q., Wang, Z., Ren, J., Wang, S., Yu, Y., Wang, R., Liu, Z., Liu, J., et al. (2024) · Developmental Cell · doi:10.1016/j.devcel.2024.02.008 · Cited by 45
Pfeifer, M., Brammeld, J. S., Price, S., Pilling, J. E., Bhavsar, D., Farcas, A. M., Bateson, J., Sundarrajan, A., Miragaia, R. J., Guan, N., et al. (2024) · Communications Biology · doi:10.1038/s42003-024-06190-w · Cited by 43
“G to generate virus 28 .”
CRISPR /Cas9‐based editing of NF‐YC4 promoters yields high‐protein rice and soybean
Wang, L., O’Conner, S., Tanvir, R., Zheng, W., Cothron, S., Towery, K., Bi, H., Ellison, E. E., Yang, B., Voytas, D. F., et al. (2024) · New Phytologist · doi:10.1111/nph.20141 · Cited by 45
“…high efficiency and high specificity for developing gene-edited, transgene-free crops (Qi et al ., 2013; Gilbert et al ., 2014; Shan et al ., 2014; Chavez et al ., 2015, 2016; Konermann et al ., 2015; Li et al. , 2012, 2017; Hu et al ., 2018; Kwon et al ., 2020; Lin et al ., 2020; Lu et al ., 2020).”
Comprehensive transcription factor perturbations recapitulate fibroblast transcriptional states
Southard, K. M., Ardy, R. C., Tang, A., O'Sullivan, D., Metzner, E., Guruvayurappan, K., & Norman, T. M. (2025) · Nature Genetics · doi:10.1038/s41588-025-02284-1 · Cited by 43
“For each atlas, cluster gene sets were derived from differentially expressed genes reported in each study (Supplementary Table 12).”
LncRNAs in vertebrates: Advances and challenges
Mallory, A. C., & Shkumatava, A. (2015) · Biochimie · doi:10.1016/j.biochi.2015.03.014 · Cited by 46
“screens [139,140], which could be used for unbiased determination of lncRNA functionality.”
BackgroundUsing CRISPR/Cas to study gene function and model disease in vivo
Tschaharganeh, D. F., Lowe, S. W., Garippa, R. J., & Livshits, G. (2016) · FEBS Journal · doi:10.1111/febs.13750 · Cited by 47
CRISPR-Mediated Epigenome Editing.
Enríquez, P. (2016) · Europe PMC (PubMed Central) · Cited by 41
Orthogonal Genetic Regulation in Human Cells Using Chemically Induced CRISPR/Cas9 Activators
Bao, Z., Jain, S., Jaroenpuntaruk, V., & Zhao, H. (2017) · ACS Synthetic Biology · doi:10.1021/acssynbio.6b00313 · Cited by 42
García‐Tuñón, I., Hernández‐Sánchez, M., Ordóñez, J. L., Alonso-Pérez, V., Quijada‐Álamo, M., Benito, R., Guerrero, C., Hernández‐Rivas, J. M., & Sánchez‐Martín, M. (2017) · Oncotarget · doi:10.18632/oncotarget.15215 · Cited by 41
Bidirectional manipulation of gene expression in adipocytes using CRISPRa and siRNA
Lundh, M., Plucińska, K., Isidor, M. S., Petersen, P. S. S., & Emanuelli, B. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.07.001 · Cited by 42
“Recently, more advanced and potent versions of the CRISPRa systems have been engineered such as the Synergistic Activation Mediator (SAM) system, in which a third component consisting of the P65 subunit of the transcription factor NF-kB and the activator domain found on heat-shock factor 1 form a complex with the dCAS…”
BackgroundPersonalised genome editing – The future for corneal dystrophies
Moore, T., Christie, K. A., Marshall, J., & Nesbit, M. A. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.01.004 · Cited by 44
“Examples of genomic safe harbours are the adeno-associated virus site (AAVS1) (Kotin et al., 1992), the chemokine (CC motif) receptor 5 (CCR5) gene locus (Lombardo et al., 2011) and the human orthologue of the mouse ROSA2g locus (Irion et al., 2007).”
BackgroundBreunig, C., Đurović, T., Neuner, A. M., Baumann, V., Wiesbeck, M. F., Köferle, A., Götz, M., Ninkovic, J., & Stricker, S. H. (2018) · PLoS ONE · doi:10.1371/journal.pone.0196015 · Cited by 42
“Shown as an example in Fig 2E is the assembly of four gRNAs, driven by four different promoter (human U6, mouse U6, 7SK and H1) and each containing additional RNA structures (one or two SAM loops) 3’ from the gRNA hairpin to allow the targeting of MS2-fusion proteins to chosen genomic sites in addition to Cas9 fusion…”
BackgroundEngineering species-like barriers to sexual reproduction
Maselko, M., Heinsch, S. C., Chacón, J. M., Harcombe, W. R., & Smanski, M. J. (2017) · Nature Communications · doi:10.1038/s41467-017-01007-3 · Cited by 42
Benhammou, J. N., Ko, A., Alvarez, M., Kaikkonen, M. U., Rankin, C. R., Garske, K. M., Padua, D. M., Bhagat, Y. V., Kamińska, D., Kärjä, V. J., et al. (2019) · Hepatology Communications · doi:10.1002/hep4.1413 · Cited by 43
“Similar to other lincRNAs, OLMALINC only shows a high homology in primates.(37) Since lincRNAs often exert their function by affecting adjacent genes, we hypothesized that OLMALINC may regulate SCD expression in cis by acting as an enhancer.”
Automated 3D light-sheet screening with high spatiotemporal resolution reveals mitotic phenotypes
Eismann, B., Krieger, T. G., Beneke, J., Bulkescher, R., Adam, L., Erfle, H., Herrmann, C., Eils, R., & Conrad, C. (2020) · Journal of Cell Science · doi:10.1242/jcs.245043 · Cited by 42
“sgRNA expression plasmids were designed and synthesized following a previously published SAM target sgRNA cloning protocol (Konermann et al., 2015).”
MethodSystematic in vitro profiling of off-target affinity, cleavage and efficiency for CRISPR enzymes
Zhang, L., Rube, H. T., Vakulskas, C. A., Behlke, M. A., Bussemaker, H. J., & Pufall, M. A. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa231 · Cited by 45
Revealing Temozolomide Resistance Mechanisms via Genome-Wide CRISPR Libraries
Rocha, C. R. R., Rocha, A. R., Silva, M. M., Gomes, L. R., Latância, M. T., Andrade-Tomaz, M., de Souza, I., Monteiro, L. K. S., & Menck, C. F. M. (2020) · Cells · doi:10.3390/cells9122573 · Cited by 42
“These cells were transduced with CRISPRa library, which targets the 200 bp region upstream of the transcriptional start site of 23,430 human coding isoforms with three sgRNAs per gene—a total of 70,290 unique sgRNAs—prioritizing sgRNAs with minimal off-target activity [16].”
BackgroundMethodLi, X., Huang, L., Pan, L., Wang, B., & Pan, L. (2021) · Microbiological Research · doi:10.1016/j.micres.2020.126694 · Cited by 42
Ren, C., Li, H., Liu, Y., Li, S., & Liang, Z. (2022) · Horticulture Research · doi:10.1093/hr/uhab037 · Cited by 42
“The results are consistent with the findings reported in previous studies [8, 13, 36, 37].”
ResultMapping the Pathways of Resistance to Targeted Therapies
Wood, K. C. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-1248 · Cited by 41
“Cancer Res; 75(20) October 15, 2015 Cancer Research 4250 Wood”
InfluentialRational design of a compact CRISPR-Cas9 activator for AAV-mediated delivery
Vora, S., Cheng, J., Xiao, R., VanDusen, N. J., Quintino, L., Pu, W. T., Vandenberghe, L. H., Chavez, A., & Church, G. (2018) · doi:10.1101/298620 · Cited by 42
Qi, X., Gao, H., Lv, R., Mao, W., Zhu, J., Liu, C., Mao, L., Li, X., & Xie, C. (2022) · Plant Communications · doi:10.1016/j.xplc.2022.100449 · Cited by 41
“Although several CRISPRa tools have been described (Tanenbaum et al., 2014; Chavez et al., 2015; Konermann et al., 2015), in vivo CRISPRa has not been characterized in maize, let alone used in ECs.”
InfluentialSaunders, A. B., Huang, K. W., Vondrak, C., Hughes, C., Smolyar, K., Sen, H., Philson, A. C., Nemesh, J. C., Wysoker, A., Kashin, S., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34334-1 · Cited by 37
Nanotechnology-enabled gene delivery for cancer and other genetic diseases
Jiang, T., Gonzalez, K. M., Cordova, L. E., & Lu, J. (2023) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2023.2200246 · Cited by 45
Mukund, A. X., Tycko, J., Allen, S. J., Robinson, S. A., Andrews, C. J., Sinha, J., Ludwig, C., Spees, K., Bassik, M. C., & Bintu, L. (2023) · Cell Systems · doi:10.1016/j.cels.2023.07.001 · Cited by 41
Synthetic biology — application-oriented cell engineering
Xie, M., Haellman, V., & Fussenegger, M. (2016) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2016.04.005 · Cited by 41
Current application of CRISPR/Cas9 gene-editing technique to eradication of HIV/AIDS
Huang, Z., Tomitaka, A., Raymond, A., & Nair, M. (2017) · Gene Therapy · doi:10.1038/gt.2017.35 · Cited by 43
Mechanisms of Long Non-Coding RNAs in the Assembly and Plasticity of Neural Circuitry
Wang, A., Wang, J., Liu, Y., & Zhou, Y. (2017) · Frontiers in Neural Circuits · doi:10.3389/fncir.2017.00076 · Cited by 42
“, 2015); as well as for repressing (CRISPRi) or inducing (CRISPRa) gene expressions without altering genomic sequences (Gilbert et al., 2013, 2014; Konermann et al., 2014).”
BackgroundChen, C.-D., Zeldich, E., Li, Y., Yuste, A., & Abraham, C. R. (2018) · Journal of Molecular Neuroscience · doi:10.1007/s12031-017-1011-0 · Cited by 41
“A nuclease-deficient Cas9 (dCas9) and the VP64 fusion transcription activator in complex with guide RNA (gRNA) is used to specifically activate single or multiple genes simultaneously (Gersbach and Perez-Pinera 2014; Kearns et al. 2014; Konermann et al. 2015).”
BackgroundMethodInfluentialLong noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function
Josipovic, I., Pflüger, B., Fork, C., Vasconez, A. E., Oo, J. A., Hitzel, J., Seredinski, S., Gamen, E., zu Heringdorf, D. M., Chen, W., et al. (2018) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2018.01.015 · Cited by 41
Wang, D., Lü, R., Rempała, G. A., & Sadée, W. (2019) · Molecular Pharmacology · doi:10.1124/mol.119.116897 · Cited by 43
Trigg, R. M., Lee, L. C., Prokoph, N., Jahangiri, L., Reynolds, C. P., Burke, G. A. A., Probst, N. A., Han, M., Matthews, J. D., Lim, H. K., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13315-x · Cited by 41
CRISPR-Switch regulates sgRNA activity by Cre recombination for sequential editing of two loci
Chylinski, K., Hubmann, M., Hanna, R. E., Yanchus, C., Michlits, G., Uijttewaal, E. C. H., Doench, J. G., Schramek, D., & Elling, U. (2019) · Nature Communications · doi:10.1038/s41467-019-13403-y · Cited by 40
CRISPR screen in mechanism and target discovery for cancer immunotherapy
Liu, D., Zhao, X., Tang, A., Xu, X., Liu, S., Zha, L., Ma, W., Zheng, J., & Shi, M. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188378 · Cited by 44
Wang, A. S., Chen, L. C., Wu, R. A., Hao, Y., McSwiggen, D. T., Heckert, A. B., Richardson, C. D., Gowen, B. G., Kazane, K. R., Vu, J. T., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.06.014 · Cited by 42
“Fusing various effector proteins to dCas9 has enabled CRISPR-based methods to activate or repress gene expression, manipulate the three-dimensional architecture of nuclei, image genomic loci, track RNA molecules, and identify proteins at specific loci (Chen et al., 2013; Gao et al., 2018; Gilbert et al., 2013; Hilton…”
BackgroundExploiting CRISPR Cas9 in Three-Dimensional Stem Cell Cultures to Model Disease
Gopal, S., Rodrigues, A. L., & Dordick, J. S. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00692 · Cited by 46
Evidence for and localization of proposed causative variants in cattle and pig genomes
Johnsson, M., & Jungnickel, M. K. (2021) · Genetics Selection Evolution · doi:10.1186/s12711-021-00662-x · Cited by 43
Naranjo, S., Cabana, C. M., LaFave, L. M., Romero, R., Shanahan, S.-L., Bhutkar, A. J., Westcott, P. M. K., Schenkel, J. M., Ghosh, A., Liao, L. Z., et al. (2022) · Genes & Development · doi:10.1101/gad.349659.122 · Cited by 42
A benchmarked, high-efficiency prime editing platform for multiplexed dropout screening
Cirincione, A., Simpson, D., Yan, W., McNulty, R., Ravisankar, P., Solley, S. C., Yan, J., Lim, F., Farley, E. K., Singh, M., et al. (2024) · Nature Methods · doi:10.1038/s41592-024-02502-4 · Cited by 42
“…and can generate reproducible, growth-based negative selection phenotypes in large, pooled experiments, achieving a reasonable rate of phenotype induction across codons in essential genes targeted with nonsense mutations (50.8% of codons by day 28 with at least one epegRNA out of multiple tested).”
InfluentialCRISPR‐Cas: From the Bacterial Adaptive Immune System to a Versatile Tool for Genome Engineering
Kirchner, M., & Schneider, S. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201504741 · Cited by 39
CRISPR‐Cas9 systems: versatile cancer modelling platforms and promising therapeutic strategies
Wen, W., Yuan, Z., Ma, S., Jiang, X., & Yuan, D. (2015) · International Journal of Cancer · doi:10.1002/ijc.29626 · Cited by 41
“sgRNA scaffolds (also called scRNAs(20)) can greatly increase regulatory efficiency(19,20) due to synergic effects with effectors directly fused to dCas9.(19) Moreover, scRNAs allow distinct regulatory events to take place at different loci simultaneously.”
BackgroundCRISPR-Cas9: from Genome Editing to Cancer Research
Chen, S., Sun, H., Miao, K., & Deng, C. (2016) · International Journal of Biological Sciences · doi:10.7150/ijbs.17421 · Cited by 40
“Besides loss-of-function screening by CRISPR-Cas9 system, several studies provide genomic screening for gain-of-function, such as transcriptional activation or activation of enhancers [67-69].”
BackgroundSphingosine kinase 1: A novel independent prognosis biomarker in hepatocellular carcinoma
Cai, H., Xie, X., Ji, L., Ruan, X., & Zheng, Z. (2017) · Oncology Letters · doi:10.3892/ol.2017.5732 · Cited by 40
CRISPR/Cas9 editing of the genome for cancer modeling
Guernet, A. A., & Grumolato, L. (2017) · Methods · doi:10.1016/j.ymeth.2017.03.007 · Cited by 44
Yeast genetic interaction screens in the age of CRISPR/Cas
Adames, N. R., Gallegos, J. E., & Peccoud, J. (2018) · Current Genetics · doi:10.1007/s00294-018-0887-8 · Cited by 36
Kunii, A., Hara, Y., Takenaga, M., Hattori, N., Fukazawa, T., Ushijima, T., Yamamoto, T., & Sakuma, T. (2018) · The CRISPR Journal · doi:10.1089/crispr.2018.0009 · Cited by 40
“Third, both the sufficient level of transcriptional activation to induce protein upregulation and a ceiling to the level of transcriptional activation regardless of the basal expression of the target transcript, observed in the previous paper, 10 were not examined in the context of this study.”
Blanas, A., Cornelissen, L. A. M., Kotsias, M., van der Horst, J. C., van de Vrugt, H. J., Kalay, H., Spencer, D. I. R., Kozak, R. P., & van Vliet, S. J. (2018) · Glycobiology · doi:10.1093/glycob/cwy096 · Cited by 39
Elucidating the mechanism of action of domatinostat (4SC-202) in cutaneous T cell lymphoma cells
Wobser, M., Weber, A., Glunz, A., Tauch, S., Seitz, K., Butelmann, T., Hesbacher, S., Goebeler, M., Bartz, R., Kohlhof, H., et al. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0719-4 · Cited by 41
Ma, Q., Yang, F., Mackintosh, C., Jayani, R. S., Oh, S., Jin, C., Nair, S. J., Merkurjev, D., Ma, W., Allen, S., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2020.107532 · Cited by 37
Exploiting the CRISPR‐Cas9 gene‐editing system for human cancers and immunotherapy
Afolabi, L. O., Afolabi, M. O., Sani, M. M., Okunowo, W. O., Yan, D., Chen, L., Zhang, Y., & Wan, X. (2021) · Clinical & Translational Immunology · doi:10.1002/cti2.1286 · Cited by 46
“Based on this approach, a novel mutation that elicits resistance against the PLX4720 (a potent and selective inhibitor of BRAF) in melanoma cells was identified.(33) These genome screenings have a lot of potential because they allow for the identification of epigenetic marks within the cancer genome when combined with…”
BackgroundETV7 limits antiviral gene expression and control of influenza viruses
Froggatt, H. M., Harding, A. T., Heaton, B. E., & Heaton, N. S. (2021) · Science Signaling · doi:10.1126/scisignal.abe1194 · Cited by 44
Genome engineering of stem cell organoids for disease modeling
Sun, Y., & Ding, Q. (2017) · Protein & Cell · doi:10.1007/s13238-016-0368-0 · Cited by 39
“For instance, screens have been performed to dissect genes or signaling pathways involved in the development of tumor drug resistance (Koike-Yusa et al., 2014; Konermann et al., 2015; Gilbert et al., 2014; Shalem et al., 2014; Wang et al., 2014; Zhou et al., 2014), transformation and metastasis of cancer cells (Chen e…”
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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