The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source doesn’t support the claim as written.
In the citing paper
“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]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Flagged first, then by citations
Cited by
Sorted by citations
Items 501–600 of 1,005
Allen, D. G., Rosenberg, M., & Hendel, A. (2021) · Frontiers in Genome Editing · doi:10.3389/fgeed.2020.617910 · Cited by 89
Peruzzi, J. A., Gunnels, T. F., Edelstein, H. I., Lu, P., Baker, D. A., Leonard, J. N., & Kamat, N. P. (2024) · Nature Communications · doi:10.1038/s41467-024-49678-z · Cited by 91
“BlastR was sourced from lenti dCAS-VP64_Blast, which was a gift from Feng Zhang (Addgene plasmid #61425) 66 .”
Gene Editing With CRISPR/Cas9 RNA-Directed Nuclease
Doetschman, T., & Georgieva, T. G. (2017) · Circulation Research · doi:10.1161/circresaha.116.309727 · Cited by 91
Williams, R. M., Senanayake, U., Artibani, M., Taylor, G., Wells, D., Ahmed, A., & Sauka-Spengler, T. (2018) · Development · doi:10.1242/dev.160333 · Cited by 77
“Here, we use a dCas9-VP64 fusion in conjunction with the synergistic activation mediator (SAM) system (Konermann et al., 2015).”
MethodDammert, M. A., Brägelmann, J., Olsen, R. R., Böhm, S., Monhasery, N., Whitney, C. P., Chalishazar, M. D., Tumbrink, H. L., Guthrie, M. R., Klein, S., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11371-x · Cited by 82
CRISPR–Cas9 Gene Editing: Curing Genetic Diseases by Inherited Epigenetic Modifications
Kolanu, N. D. (2024) · Global Medical Genetics · doi:10.1055/s-0044-1785234 · Cited by 93
“Konermann et al. 36 Histone Methylation Histone methyltransferases or demethylases can be coupled with dCAS9 to methylate or demethylate certain histone residues, resulting in the desired transcriptional changes.”
BackgroundEfficient Transcriptional Gene Repression by Type V-A CRISPR-Cpf1 from Eubacterium eligens
Kim, S. K., Kim, H., Ahn, W., Park, K., Woo, E., Lee, D., & Lee, S. (2017) · ACS Synthetic Biology · doi:10.1021/acssynbio.6b00368 · Cited by 81
Genetic and epigenetic control of gene expression by CRISPR–Cas systems
Lo, A., & Qi, L. (2017) · F1000Research · doi:10.12688/f1000research.11113.1 · Cited by 72
“This method is referred to as the synergistic activation mediator (SAM) system (Figure 2B) 75 .”
BackgroundMethodImaging Specific Genomic DNA in Living Cells
Chen, B., Guan, J., & Huang, B. (2016) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-062215-010830 · Cited by 77
“This approach has been successfully used for genomic regulatory programming by recruiting regulatory domains to target loci through scRNAs (74, 90, 154).”
MethodYe, L., Wang, C., Hong, L., Sun, N., Chen, D., Chen, S., & Han, F. (2018) · Cell Discovery · doi:10.1038/s41421-018-0049-7 · Cited by 83
Functions of the COPII gene paralogs SEC23A and SEC23B are interchangeable in vivo
Khoriaty, R. N., Hesketh, G. G., Bernard, A., Weyand, A. C., Mellacheruvu, D., Zhu, G., Hoenerhoff, M. J., McGee, B. M., Everett, L. A., Adams, E., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1805784115 · Cited by 82
The COMET toolkit for composing customizable genetic programs in mammalian cells
Donahue, P. S., Draut, J. W., Muldoon, J. J., Edelstein, H. I., Bagheri, N., & Leonard, J. N. (2020) · Nature Communications · doi:10.1038/s41467-019-14147-5 · Cited by 78
Insights Into Genetic and Molecular Elements for Transgenic Crop Development
Basso, M. F., Arraes, F. B. M., Grossi-De-Sá, M. F., Moreira, V. J. V., Alves‐Ferreira, M., & Grossi‐de‐Sá, M. F. (2020) · Frontiers in Plant Science · doi:10.3389/fpls.2020.00509 · Cited by 84
Photoactivatable RNA N6‐Methyladenosine Editing with CRISPR‐Cas13
Zhao, J., Li, B., Ma, J., Jin, W., & Ma, X. (2020) · Small · doi:10.1002/smll.201907301 · Cited by 81
The long non-coding RNA LUCAT1 is a negative feedback regulator of interferon responses in humans
Agarwal, S., Vierbuchen, T., Ghosh, S., Chan, J., Jiang, Z., Kandasamy, R. K., Ricci, E. P., & Fitzgerald, K. A. (2020) · Nature Communications · doi:10.1038/s41467-020-20165-5 · Cited by 82
Hijacking of transcriptional condensates by endogenous retroviruses
Asimi, V., Kumar, A. S., Niskanen, H., Riemenschneider, C., Hetzel, S., Naderi, J., Fasching, N., Popitsch, N. P., Du, M., Kretzmer, H., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01132-w · Cited by 79
Recent Advances in CRISPR-Cas Technologies for Synthetic Biology
Jeong, S. H., Lee, H. J., & Lee, S. J. (2023) · The Journal of Microbiology · doi:10.1007/s12275-022-00005-5 · Cited by 88
Design, execution, and analysis of pooled in vitro CRISPR /Cas9 screens
Miles, L. A., Garippa, R. J., & Poirier, J. T. (2016) · FEBS Journal · doi:10.1111/febs.13770 · Cited by 78
New directions for improving crop resistance to insects by breeding for egg induced defence
Tamiru, A., Khan, Z. R., & Bruce, T. J. A. (2015) · Current Opinion in Insect Science · doi:10.1016/j.cois.2015.02.011 · Cited by 80
Ji, H., Jiang, Z., Lu, P., Ma, L., Li, C., Pan, H., Fu, Z., Qu, X., Wang, P., Deng, J., et al. (2016) · Molecular Therapy · doi:10.1038/mt.2016.7 · Cited by 80
CRISPR system in filamentous fungi: Current achievements and future directions
Deng, H., Gao, R., Liao, X., & Cai, Y. (2017) · Gene · doi:10.1016/j.gene.2017.06.019 · Cited by 81
Application of the CRISPR/Cas system for genome editing in microalgae
Zhang, Y., Jiang, J., Shi, T., Sun, X., Zhao, Q., Huang, H., & Ren, L. (2019) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-019-09726-x · Cited by 82
Truong, V. A., Hsu, M., Nguyen, N. T. K., Lin, M., Shen, C., Lin, C., & Hu, Y. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz267 · Cited by 78
“(13) developed a synergistic activation mediator (SAM) system that comprises (i) dCas9-VP64, (ii) engineered sgRNA containing two copies of MS2 RNA hairpin that interacts with MS2 coat protein (MCP), and (iii) MPH fusion protein comprising MCP, p65 and heat shock factor 1 (HSF1) as the activation complex.”
BackgroundMethodInfluentialTranscriptional control by enhancers and enhancer RNAs
Lewis, M. W., Shen, L., & Franco, H. L. (2019) · Transcription · doi:10.1080/21541264.2019.1695492 · Cited by 84
“[184] Konermann S, Brigham MD, Trevino AE, et al.”
BackgroundLi, C., Zong, Y., Jin, S., Zhu, H., Lin, D., Li, S., Qiu, J., Wang, Y., & Gao, C. (2020) · Genome biology · doi:10.1186/s13059-020-02051-x · Cited by 80
“0) were generated for comparison [18, 24] (Fig.”
Thermoreversible Control of Nucleic Acid Structure and Function with Glyoxal Caging
Knutson, S. D., Sanford, A. A., Swenson, C., Korn, M. M., Manuel, B. A., & Heemstra, J. M. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c08996 · Cited by 79
Synthetic biology in cell-based cancer immunotherapy
Chakravarti, D., & Wong, W. W. (2015) · Trends in biotechnology · doi:10.1016/j.tibtech.2015.05.001 · Cited by 80
Lack of Transcription Triggers H3K27me3 Accumulation in the Gene Body
Hosogane, M., Funayama, R., Shirota, M., & Nakayama, K. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.034 · Cited by 82
Directed Enzyme Evolution: Advances and Applications
Alcalde, M. (2017) · Springer eBooks · doi:10.1007/978-3-319-50413-1 · Cited by 81
Optimized strategy for in vivo Cas9-activation in Drosophila
Ewen‐Campen, B., Yang‐Zhou, D., Fernandes, V. R., González, D. P., Liu, L., Tao, R., Ren, X., Sun, J., Hu, Y., Zirin, J. D., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1707635114 · Cited by 78
“Based on our previous observations, we generated transgenic flies expressing two sgRNAs per target gene, targeting a window between −400 and 0 bp upstream of the TSS (8).”
BackgroundMethodInfluentialEngineering Synthetic Signaling Pathways with Programmable dCas9-Based Chimeric Receptors
Baeumler, T. A., Ahmed, A. A., & Fulga, T. A. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.044 · Cited by 79
Gómez-García, P. A., Portillo‐Ledesma, S., Neguembor, M. V., Pesaresi, M., Oweis, W., Rohrlich, T. M., Wieser, S., Meshorer, E., Tamar Schlick, A., Cosma, M. P., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108614 · Cited by 76
“3) into pLENTI-dCas9-VP64_GFP backbone (Konermann et al., 2015).”
InfluentialGenome-wide CRISPR activation screen identifies candidate receptors for SARS-CoV-2 entry
Zhu, S., Liu, Y., Zhou, Z. L., Zhang, Z., Xiao, X., Liu, Z., Chen, A., Dong, X., Tian, F., Chen, S., et al. (2021) · Science China Life Sciences · doi:10.1007/s11427-021-1990-5 · Cited by 78
Zhou, X., Updegraff, B. L., Guo, Y., Peyton, M., Girard, L., Larsen, J. E., Xie, X., Zhou, Y., Hwang, T. H., Xie, Y., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-1267-t · Cited by 75
Three-dimensional genome architecture and emerging technologies: looping in disease
Mishra, A., & Hawkins, R. D. (2017) · Genome Medicine · doi:10.1186/s13073-017-0477-2 · Cited by 79
A CRISPR Activation Screen Identifies Genes That Protect against Zika Virus Infection
Dukhovny, A., Lamkiewicz, K., Chen, Q., Fricke, M., Jabrane‐Ferrat, N., Marz, M., Jung, J. U., & Sklan, E. H. (2019) · Journal of Virology · doi:10.1128/jvi.00211-19 · Cited by 78
“Since the library contains 70,290 sgRNAs, this number is sufficient for infection of at least 500 cells with each sgRNA (12, 21).”
BackgroundMethodGenome-scale CRISPR pooled screens
Sanjana, N. E. (2016) · Analytical Biochemistry · doi:10.1016/j.ab.2016.05.014 · Cited by 81
Next stop for the CRISPR revolution: RNA‐guided epigenetic regulators
Vora, S., Tuttle, M. L., Cheng, J. Y., & Church, G. M. (2016) · FEBS Journal · doi:10.1111/febs.13768 · Cited by 75
CRISPR/Cas: From Tumor Gene Editing to T Cell-Based Immunotherapy of Cancer
Azangou‐Khyavy, M., Ghasemi, M., Khanali, J., Boroomand-Saboor, M., Jamalkhah, M., Soleimani, M., & Kiani, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02062 · Cited by 80
“effectors are recruited by both dCas and scRNA (208).”
BackgroundTao, Y., Yi, K., Hu, H., Shao, D., & Li, M. (2020) · Journal of Materials Chemistry B · doi:10.1039/d0tb01925a · Cited by 78
Enhancement of specialized metabolites using CRISPR/Cas gene editing technology in medicinal plants
Das, S., Kwon, M., & Kim, J. (2024) · Frontiers in Plant Science · doi:10.3389/fpls.2024.1279738 · Cited by 82
A genome-wide atlas of human cell morphology
Ramezani, M., Weisbart, E., Bauman, J., Singh, A. K., Yong, J., Lozada, M., Way, G. P., Kavari, S. L., Diaz, C., Leardini, E., et al. (2025) · Nature Methods · doi:10.1038/s41592-024-02537-7 · Cited by 74
“In its current form, the PERISCOPE platform could be deployed to explore the effects of other CRISPR-based perturbations such as CRISPR-a 59,60 , CRISPR-i 61,62 or base editing 63–65 , where sgRNAs can be expressed as an RNA Pol II transcript (as in CROP-seq).”
Efficient Gene Disruption in Cultured Primary Human Endothelial Cells by CRISPR/Cas9
Abrahimi, P., Chang, W., Kluger, M. S., Qyang, Y., Tellides, G., Saltzman, W. M., & Pober, J. S. (2015) · Circulation Research · doi:10.1161/circresaha.117.306290 · Cited by 81
Unraveling the 3D genome: genomics tools for multiscale exploration
Risca, V. I., & Greenleaf, W. J. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.03.010 · Cited by 77
“The CRISPR/Cas9 system and TAL effector domains have been developed as a platform for designing artificial transcriptional activators or repressors targeted to any sequence [176–178].”
BackgroundTransposons As Tools for Functional Genomics in Vertebrate Models
Kawakami, K., Largaespada, D. A., & Ivics, Z. (2017) · Trends in Genetics · doi:10.1016/j.tig.2017.07.006 · Cited by 77
In vivo locus-specific editing of the neuroepigenome
Yim, Y. Y., Teague, C. D., & Nestler, E. J. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-0334-y · Cited by 76
Applications of CRISPR Genome Engineering in Cell Biology
Wang, F., & Qi, L. S. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.08.004 · Cited by 79
“These include recruiting multiple copies of the VP64 domain via a multimeric peptide array (SunTag), wherein each peptide domain could bind to a single-chain variable fragment (scFv) fused to VP64 [64]; fusing dCas9 to a synergistic tripartite activator system containing VP64, the activation domain of p65 (p65AD), and…”
Development and application of CRISPR/Cas9 technologies in genomic editing
Zhang, C., Quan, R., & Wang, J. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy120 · Cited by 80
Ng, S. R., Rideout, W. M., Akama‐Garren, E. H., Bhutkar, A. J., Mercer, K. L., Schenkel, J. M., Bronson, R. T., & Jacks, T. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1821893117 · Cited by 78
Modulating gene regulation to treat genetic disorders
Matharu, N. K., & Ahituv, N. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0083-7 · Cited by 79
Liu, R., Yang, J., Yao, J., Zhao, Z., He, W., Su, N., Zhang, Z., Zhang, C., Zhang, Z., Cai, H., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-021-01112-1 · Cited by 76
CRISPR–Cas9 a boon or bane: the bumpy road ahead to cancer therapeutics
Ghosh, D., Venkataramani, P., Nandi, S., & Bhattacharjee, S. (2019) · Cancer Cell International · doi:10.1186/s12935-019-0726-0 · Cited by 83
Expanding C–T base editing toolkit with diversified cytidine deaminases
Cheng, T., Li, S., Yuan, B., Wang, X., Zhou, W., & Qiu, Z. (2019) · Nature Communications · doi:10.1038/s41467-019-11562-6 · Cited by 74
Haikala, H. M., Anttila, J. M., Marques, E., Raatikainen, T., Ilander, M. M., Hakanen, H. H. E., Ala-Hongisto, H., Savelius, M., Balboa, D., von Eyß, B., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08541-2 · Cited by 73
Development and Application of CRISPR/Cas in Microbial Biotechnology
Ding, W., Zhang, Y., & Shi, S. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00711 · Cited by 81
Russo, G. L., Sonsalla, G., Natarajan, P., Breunig, C., Bulli, G., Merl‐Pham, J., Schmitt, S., Giehrl‐Schwab, J., Giesert, F., Jastroch, M., et al. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.10.015 · Cited by 78
“…transactivating domains (VP64, p65, and RTA[R transactivator]) and SAM (synergistic activator Mediator) components (dCAM) (Chavez et al., 2015; Konermann et al., 2015; STAR Methods) with the astrocyte-specific Aldh1l1:- Cre mouse line (Tien et al., 2012; Figure 3B), were co-transfected with…”
Black, J. B., McCutcheon, S. R., Dube, S., Barrera, A., Klann, T. S., Rice, G., Adkar, S. S., Soderling, S. H., Reddy, T. E., & Gersbach, C. A. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108460 · Cited by 71
“The degree of TF induction directly correlated with the basal expression level of the target gene, consistent with previous reports (Konermann et al., 2015) (Figure S3B).”
Golden Gate Assembly of CRISPR gRNA expression array for simultaneously targeting multiple genes
Vad‐Nielsen, J., Lin, L., Bolund, L., Nielsen, A. L., & Luo, Y. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2271-5 · Cited by 72
Kurata, M., Rathe, S. K., Bailey, N. J., Aumann, N. K., Jones, J. M., Veldhuijzen, G. W., Moriarity, B. S., & Largaespada, D. A. (2016) · Scientific Reports · doi:10.1038/srep36199 · Cited by 74
“As our screen only identified DCK as a candidate Ara-C resistance gene and defective DCK is already a known mechanism of Ara-C resistance 4,8,9 , we decided to remove the ability of the CRISPR library to knock out DCK .”
Field, A. R., Jacobs, F. M. J., Fiddes, I. T., Phillips, A. P. R., Reyes-Ortiz, A. M., LaMontagne, E., Whitehead, L., Meng, V., Rosenkrantz, J. L., Olsen, M. N., et al. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.12.006 · Cited by 75
“, 2008), we assessed potential TrEx lncRNA gene regulatory function by CRISPRa using dCas9-VP64 to drive transcription at the endogenous locus in HEK293FT cells (Konermann et al., 2014), thus allowing detection of either mode of action.”
MethodCutting back malaria: CRISPR/Cas9 genome editing of Plasmodium
Lee, M., Lindner, S. E., Lopez-Rubio, J.-J., & Llinás, M. (2019) · Briefings in Functional Genomics · doi:10.1093/bfgp/elz012 · Cited by 78
“Beyond simple steric interference, however, dCas9 has become a sophisticated platform for targeted delivery to genomic sites of a variety of addon effector domains, either via direct fusion with dCas9, recruitment to a dCas9-linked epitope array such as the SunTag [49], or by using a modified gRNA that presents a prot…”
BackgroundAngptl8 mediates food-driven resetting of hepatic circadian clock in mice
Chen, S., Feng, M., Zhang, S., Dong, Z., Wang, Y., Zhang, W., & Liu, C. (2019) · Nature Communications · doi:10.1038/s41467-019-11513-1 · Cited by 74
A green tea–triggered genetic control system for treating diabetes in mice and monkeys
Yin, J., Yang, L., Mou, L., Dong, K., Jiang, J. D., Xue, S., Xu, Y. C., Wang, X., Lu, Y., & Ye, H. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aav8826 · Cited by 74
lncRNAs: function and mechanism in cartilage development, degeneration, and regeneration
Zhu, J., Yu, W., Wang, Y., Xia, K., Huang, Y., Xu, A., Chen, Q., Liu, B., Tao, H., Li, F., et al. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1458-8 · Cited by 75
“Therefore, the derivative of Cas9 should be developed to remove the entire gene fragments [139, 140].”
BackgroundJing, Y., Jiang, X., Ji, Q., Wu, Z., Wang, W., Liu, Z., Guillén-García, P., Esteban, C. R., Reddy, P., Horvath, S., et al. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.09.007 · Cited by 77
“33 This approach directly and endogenously activates the expression of individual genes in a single-gene-per-cell manner with sgRNAs targeting the transcriptional start sites (TSSs) of different genes simultaneously in a pooled screen, which makes it more scalable and accessible than conventional…”
BackgroundDrug-tunable multidimensional synthetic gene control using inducible degron-tagged dCas9 effectors
Kleinjan, D. A., Wardrope, C., Sou, S. N., & Rosser, S. J. (2017) · Nature Communications · doi:10.1038/s41467-017-01222-y · Cited by 74
Functional genomics to uncover drug mechanism of action
Nijman, S. M. B. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1963 · Cited by 75
Samarajeewa, A., Jacques, B. E., & Dabdoub, A. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.03.017 · Cited by 73
Perenthaler, E., Yousefi, S., Niggl, E., & Barakat, T. S. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00352 · Cited by 75
“…et al., 2013; Mali et al., 2013), the nuclear factor-κB (NF-κB) trans-activating subunit activation domain (p65) and human heat-shock factor 1 (HSF1) (Konermann et al., 2015), the 10–11 translocation methylcytosine dioxygenase 1 (TET1) (Liu X. S. et al., 2016), and the p300 acetyltransferase…”
BackgroundSynthetic Biology on Acetogenic Bacteria for Highly Efficient Conversion of C1 Gases to Biochemicals
Jin, S., Bae, J., Song, Y., Pearcy, N., Shin, J., Kang, S., Minton, N. P., Soucaille, P., & Cho, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207639 · Cited by 73
“Although CRISPR activation (CRISPRa) activates targeted gene expression with the assistance of transcription activators in other organisms [137,138], a lack of well-characterized activators suitable for bacteria has impeded CRISPRa applications in non-model organisms.”
BackgroundRamms, D. J., Raimondi, F., Arang, N., Herberg, F. W., Taylor, S. S., & Gutkind, J. S. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000269 · Cited by 73
CRISPR/Cas9-The ultimate weapon to battle infectious diseases?
Doerflinger, M., Forsyth, W. O., Ebert, G., Pellegrini, M., & Herold, M. J. (2016) · Cellular Microbiology · doi:10.1111/cmi.12693 · Cited by 73
de la Fuente‐Núñez, C., & Lu, T. K. (2016) · Integrative Biology · doi:10.1039/c6ib00140h · Cited by 75
Long Non-Coding RNAs in Thyroid Cancer: Implications for Pathogenesis, Diagnosis, and Therapy
Mahmoudian‐Sani, M., Jalali, A., Jamshidi, M., Moridi, H., Alghasi, A., Shojaeian, A., & Mobini, G. R. (2019) · Oncology Research and Treatment · doi:10.1159/000495151 · Cited by 72
Enhancement of Precise Gene Editing by the Association of Cas9 With Homologous Recombination Factors
Tran, N. T., Bashir, S., Li, X., Rossius, J., Chu, V. T., Rajewsky, K., & Kühn, R. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00365 · Cited by 77
“Using CtIP, we compared the direct fusion with Cas9 to alternative molecular configurations that associate CtIP with guide RNA that includes MS2 binding loops (Figure 1C) or with a Cas9-SunTag fusion protein (Figure 1D), previously developed for binding of transcriptional activators to dCas9 (Tanenbaum et al., 2014; K…”
BackgroundFunctional Genomics for Cancer Drug Target Discovery
Haley, B., & Roudnicky, F. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.04.006 · Cited by 75
A versatile, high-efficiency platform for CRISPR-based gene activation
Heidersbach, A. J., Dorighi, K. M., Gomez, J. A., Jacobi, A. M., & Haley, B. (2023) · Nature Communications · doi:10.1038/s41467-023-36452-w · Cited by 72
Targeted Gene Manipulation in Plants Using the CRISPR/Cas Technology
Zhang, D., Li, Z., & Li, J.-F. (2016) · Journal of Genetics and Genomics · doi:10.1016/j.jgg.2016.03.001 · Cited by 67
Modulating the expression of long non‐coding RNAs for functional studies
Liu, S. J., & Lim, D. A. (2018) · EMBO Reports · doi:10.15252/embr.201846955 · Cited by 74
“By localizing gene activation domains such as VP64 just upstream of the TSS of lncRNAs (or any other gene transcribed by RNA polymerase II) [91,93,95], lncRNA genes can be specifically overexpressed [94].”
A CRISPR Interference Platform for Efficient Genetic Repression in Candida albicans
Wensing, L. F., Sharma, J., Uthayakumar, D., Proteau, Y., Chavez, A., & Shapiro, R. S. (2019) · mSphere · doi:10.1128/msphere.00002-19 · Cited by 71
Hsu, M., Liao, H.-T., Truong, V. A., Huang, K.-L., Yu, F.-J., Chen, H., Nguyen, T. K. N., Макаревич, П. И., Parfyonova, Y. V., & Hu, Y.-C. (2019) · Theranostics · doi:10.7150/thno.36790 · Cited by 71
“In parallel, the MCP-p65-HSF1 (MPH) fusion gene was PCR-amplified from pMS2-P65-HSF1_GFP (Addgene #61423 [22]) with a porcine teschovirus-1 2A (P2A) sequence at the 5’ end.”
InfluentialCRISPR-based metabolic pathway engineering
Zhao, D., Zhu, X., Zhou, H., Sun, N., Wang, T., Bi, C., & Zhang, X. (2020) · Metabolic Engineering · doi:10.1016/j.ymben.2020.10.004 · Cited by 70
Directed evolution and synthetic biology applications to microbial systems
Bassalo, M. C., Liu, R., & Gill, R. T. (2016) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2016.03.016 · Cited by 72
Pooled extracellular receptor-ligand interaction screening using CRISPR activation
Chong, Z., Ohnishi, S., Yusa, K., & Wright, G. J. (2018) · Genome biology · doi:10.1186/s13059-018-1581-3 · Cited by 71
Xue, Z., Cui, C., Liao, Z., Xia, S., Zhang, P., Qin, J., Guo, Q., Chen, S., Fu, Q., Yin, Z., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02967 · Cited by 71
“As CRISPR/dCas9-VP64 vector system could be applied to up-regulate gene transcription in situ (41, 42), we constructed CRISPR/dCas9-VP64 vector system by designing a sgRNA targeting linc00513 promoter region to effectively promote linc00513 transcription.”
MethodGenetic screening for single-cell variability modulators driving therapy resistance
Torre, E. A., Arai, E., Bayatpour, S., Jiang, C., Beck, L. E., Emert, B. L., Shaffer, S. M., Mellis, I. A., Fane, M. E., Alicea, G. M., et al. (2021) · Nature Genetics · doi:10.1038/s41588-020-00749-z · Cited by 71
Genetic dissection of mammalian ERAD through comparative haploid and CRISPR forward genetic screens
Timms, R. T., Menzies, S. A., Tchasovnikarova, I. A., Christensen, L. C., Williamson, J. C., Antrobus, R., Dougan, G., Ellgaard, L., & Lehner, P. J. (2016) · Nature Communications · doi:10.1038/ncomms11786 · Cited by 68
Rui, Y., Varanasi, M., Mendes, S., Yamagata, H. M., Wilson, D. R., & Green, J. J. (2020) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2020.04.005 · Cited by 71
Emerging landscape of cell penetrating peptide in reprogramming and gene editing
Liu, H., Zeng, F., Zhang, M. X., Huang, F., Wang, J., Guo, J., Liu, C.-B., & Wang, H. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.02.002 · Cited by 73
Gascuel, Q., Diretto, G., Monforte, A. J., Fortes, A. M., & Granell, A. (2017) · Frontiers in Plant Science · doi:10.3389/fpls.2017.00652 · Cited by 70
“A simplified CRISPR system, relying on a single protein (Cas9), has been shown capable of modulating expression of specific one-by-one targets in human cells, insects and plants (Shalem et al., 2014; Konermann et al., 2015).”
BackgroundA transcribed enhancer dictates mesendoderm specification in pluripotency
Alexanian, M., Maric, D., Jenkinson, S. P., Mina, M., Friedman, C. E., Ting, C.-C., Micheletti, R., Plaisance, I., Nemir, M., Maison, D., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01804-w · Cited by 70
The impact of CRISPR–Cas9 on target identification and validation
Moore, J. D. (2015) · Drug Discovery Today · doi:10.1016/j.drudis.2014.12.016 · Cited by 73
Khosravi, M. A., Abbasalipour, M., Concordet, J., Berg, J. V., Zeinali, S., Arashkia, A., Azadmanesh, K., Buch, T., & Karimipoor, M. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.04.042 · Cited by 71
A compact synthetic pathway rewires cancer signaling to therapeutic effector release
Chung, H. K., Zou, X., Bajar, B. T., Brand, V. R., Huo, Y., Alcudia, J. F., Ferrell, J. E., & Lin, M. Z. (2019) · Science · doi:10.1126/science.aat6982 · Cited by 69
“We constructed RASER systems for ErbB-dependent release of catalytically dead Cas9 fused to transcriptional activation domains (Cas9VP64orVPRdCas9) (27, 28) and coexpressed themwith guide RNAs (gRNAs) to target genes of interest (Fig.”
MethodLncRNA MIAT correlates with immune infiltrates and drug reactions in hepatocellular carcinoma
Peng, L., Chen, Y., Ou, Q., Wang, X., & Tang, N. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.107071 · Cited by 69
Richart, L., Picod-Chedotel, M.-L., Wassef, M. A., Macario, M., Aflaki, S., Salvador, M. A., Héry, T., Dauphin, A., Wicinski, J., Chevrier, V., et al. (2021) · Cell · doi:10.1016/j.cell.2022.04.034 · Cited by 69
Nucleic acid-assisted CRISPR-Cas systems for advanced biosensing and bioimaging
Chen, S., Gong, B., Zhu, C., Lei, C., & Nie, Z. (2023) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2023.116931 · Cited by 68
Zhao, L., Lai, Y., Jiao, H., & Huang, J. (2024) · Nature Communications · doi:10.1038/s41467-024-47633-6 · Cited by 69
“Although NGF is most commonly associated with pain, this relationship would have to be specifically investigated before this conclusion can be reached.”
APOBEC: From mutator to editor
Yang, B., Li, X., Lei, L., & Chen, J. (2017) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2017.04.009 · Cited by 70
A transcription factor addiction in leukemia imposed by the MLL promoter sequence
Lu, B., Klingbeil, O., Tarumoto, Y., Somerville, T., Huang, Y.-H., Wei, Y.-L., Wai, D. C. C., Low, J., Milazzo, J. P., Wu, X.-L. S., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.10.015 · Cited by 58
“pyogenes Cas9 linked to transcriptional activation domains, which allows for sgRNA-directed transcriptional activation of endogenous promoter regions (Konermann et al., 2015) (Figure S5A–B).”
BackgroundMethod
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
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
