The DOI matches its Crossref record; 90 of the 91 references it cites were found in a registry or an index.
Beyond editing: repurposing CRISPR-Cas9 for precision genome regulation and interrogation
Open accessAbstract
The bacterial CRISPR-Cas9 system has emerged as a multifunctional platform for sequence-specific regulation of gene expression. This Review describes the development of technologies based on nuclease-deactivated Cas9, termed dCas9, for RNA-guided genomic transcription regulation, both by repression through CRISPR interference (CRISPRi) and by activation through CRISPR activation (CRISPRa). We highlight different uses in diverse organisms, including bacterial and eukaryotic cells, and summarize current applications of harnessing CRISPR-dCas9 for multiplexed, inducible gene regulation, genome-wide screens and cell fate engineering. We also provide a perspective on future developments of the technology and its applications in biomedical research and clinical studies.
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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 [76]
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“Therefore, catalytically inactive dCas-9 can be used to activate (CRISPRa) or silence (CRISPRi) the expression of a specific gene of interest.50”
From Mechanism and Applications of CRISPR/Cas-9-Mediated Genome Editing (2021) · cites this paper as [50]
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“One general challenge for these CRISPR methods involves the specificity and efficiency of gRNAs (reviewed in [94]).”
From Mapping gene regulatory networks from single-cell omics data (2018) · cites this paper as [94]
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“As all four methods are based on CRISPR/CAS9, in principle, any CRISPR-based perturbations could be used, including knockouts and transcriptional- or epigenetic-based repression or activation (e.g. CRISPRi, CRISPRa [94]).”
From Mapping gene regulatory networks from single-cell omics data (2018) · cites this paper as [94]
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Cites
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
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339
RNA-Guided Human Genome Engineering via Cas9
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210
The new frontier of genome engineering with CRISPR-Cas9
Doudna, J. A., & Charpentier, E. (2014) · Science · doi:10.1126/science.1258096 · Cited by 7,062
CRISPR Provides Acquired Resistance Against Viruses in Prokaryotes
Barrangou, R., Fremaux, C., Deveau, H., Richards, M., Boyaval, P., Moineau, S., Romero, D. A., & Horvath, P. (2007) · Science · doi:10.1126/science.1138140 · Cited by 5,947
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
Genome-scale CRISPR-Cas9 knockout screening in human cells
Shalem, O., Sanjana, N. E., Hartenian, E., Shi, X., Scott, D. A., Mikkelsen, T. S., Heckl, D., Ebert, B. L., Root, D. E., Doench, J. G., et al. (2014) · Science · doi:10.1126/science.1247005 · Cited by 5,234
Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression
Qi, L. S., Larson, M. H., Gilbert, L. A., Doudna, J. A., Weissman, J. S., Arkin, A. P., & Lim, W. A. (2013) · Cell · doi:10.1016/j.cell.2013.02.022 · Cited by 5,016
Self-citationCpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System
Zetsche, B., Gootenberg, J. S., Abudayyeh, O. O., Slaymaker, I. M., Makarova, K. S., Essletzbichler, P., Volz, S. E., Joung, J., van der Oost, J., Regev, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.09.038 · Cited by 4,761
DNA targeting specificity of RNA-guided Cas9 nucleases
Hsu, P. D., Scott, D. A., Weinstein, J. A., Ran, F. A., Konermann, S., Agarwala, V., Li, Y., Fine, E. J., Wu, X., Shalem, O., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2647 · Cited by 4,741
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Cellular uptake of nanoparticles: Journey inside the cell
Behzadi, S., Serpooshan, V., Tao, W., Hamaly, M. A., Alkawareek, M. Y., Dreaden, E. C., Brown, D., Alkilany, A. M., Farokhzad, O. C., & Mahmoudi, M. (2017) · Chemical Society Reviews · doi:10.1039/c6cs00636a · Cited by 2,859
Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors
Anzalone, A. V., Koblan, L. W., & Liu, D. R. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0561-9 · Cited by 2,237
CRISPR–Cas9 Structures and Mechanisms
Jiang, F., & Doudna, J. A. (2017) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-062215-010822 · Cited by 2,029
CRISPR/Cas Genome Editing and Precision Plant Breeding in Agriculture
Chen, K., Wang, Y., Zhang, R., Zhang, H., & Gao, C. (2019) · Annual Review of Plant Biology · doi:10.1146/annurev-arplant-050718-100049 · Cited by 1,696
“, VP64, p65AD, and VPR) can be used for gene regulation (26) (Figure 2c).”
BackgroundInduced pluripotent stem cell technology: a decade of progress.
Shi, Y., Inoue, H., Wu, J. C., & Yamanaka, S. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.245 · Cited by 1,525
Metadata
- Authors
- Dominguez, A. A., Lim, W. A., & Qi, L. S.
- Affiliations
- Stanford University (US)
- QB3 (US)
- Corresponding author
- Lim, Wendell A.
- Qi, Lei S.
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2015-12-16
- Volume
- 17
- Issue
- 1
- Pages
- 5-15
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC4922510
- OpenAlex
- W2204875887
- Cited by
- 832
- References
- 91
- Citations by year
- 2026: 39 · 2025: 41 · 2024: 58 · 2023: 65 · 2022: 78 · 2021: 81 · 2020: 95 · 2019: 105 · 2018: 106 · 2017: 96 · 2016: 63 · 2015: 2
- FWCI
- 8.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (DP5OD017887)
- National Institute on Drug Abuse (R01DA036858)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- CRISPR/Cas9, dCas9, CRISPR interference, CRISPR activation, gene expression inhibition, gene activation, genome-wide screen
- MeSH terms
- Animals, Humans, Models, Genetic, Transcription, Genetic, Genome, RNA Editing, Genomics, CRISPR-Cas Systems
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