The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Measuring and Reducing Off-Target Activities of Programmable Nucleases Including CRISPR-Cas9
Open accessAbstract
Programmable nucleases, which include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and RNA-guided engineered nucleases (RGENs) repurposed from the type II clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system are now widely used for genome editing in higher eukaryotic cells and whole organisms, revolutionising almost every discipline in biological research, medicine, and biotechnology. All of these nucleases, however, induce off-target mutations at sites homologous in sequence with on-target sites, limiting their utility in many applications including gene or cell therapy. In this review, we compare methods for detecting nuclease off-target mutations. We also review methods for profiling genome-wide off-target effects and discuss how to reduce or avoid offtarget mutations.1 PROGRAMMABLE NUCLEASES FOR GENOME EDITINGGenome editing is a method of modifying genome sequences in cells and whole organisms via custom-designed programmable nucleases (Kim and Kim, 2014), which cleave chromosomal DNA in a targeted manner, producing site-specific DNA double-strand breaks (DSBs).These DSBs are efficiently repaired in cells by endogenous DNA repair systems known as homologous recombination (HR) and non-homologous end joining (NHEJ), often causing site-specific genome modifications.This technique is now widely used in research, medicine, and biotechnology, a phenomenon that is highlighted by the choice of genome editing as the 2011 Method of the Year and one of the 2015 Methods to Watch by Nature Methods and as a Breakthrough of the Year runner-up by Science in 2013.For example, gene knockout using engineered nucleases enables identification and validation of drug-able target genes.Gene correction in stem and somatic cells can lead to gene therapy
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Citations
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
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
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
High-Frequency off-Target Mutagenesis Induced by CRISPR-Cas Nucleases in Human Cells
Fu, Y., Foden, J. A., Khayter, C., Maeder, M. L., Reyon, D., Joung, J. K., & Sander, J. D. (2013) · Nature Biotechnology · doi:10.1038/nbt.2623 · Cited by 3,292 · cited 1×
“Indeed, RGENs can induce unwanted mutations at off-target sites that differ by up to several nucleotides from on-target sites (Cho et al., 2014; Cradick et al., 2013; Fu et al., 2013; Hsu et al., 2013).”
BackgroundIn vivo genome editing using Staphylococcus aureus Cas9
Ran, F. A., Cong, L., Yan, W. X., Scott, D. A., Gootenberg, J. S., Kriz, A. J., Zetsche, B., Shalem, O., Wu, X., Makarova, K. S., et al. (2015) · Nature · doi:10.1038/nature14299 · Cited by 2,687
GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases
Tsai, S. Q., Zheng, Z., Nguyen, N. T., Liebers, M., Topkar, V. V., Thapar, V., Wyvekens, N., Khayter, C., Iafrate, A. J., Le, L. P., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3117 · Cited by 2,268
Improving CRISPR-Cas nuclease specificity using truncated guide RNAs
Fu, Y., Sander, J. D., Reyon, D., Cascio, V. M., & Joung, J. K. (2014) · Nature Biotechnology · doi:10.1038/nbt.2808 · Cited by 1,993 · cited 1×
“Second, truncated sgRNAs (tru-sgRNAs) with 17-nt, rather than 20-nt, of complementarity enhance the specificity of RNA-guided genome editing (Fu et al., 2014).”
BackgroundTargeted genome engineering in human cells with the Cas9 RNA-guided endonuclease
Cho, S. W., Kim, S., Kim, J. M., & Kim, J.-S. (2013) · Nature Biotechnology · doi:10.1038/nbt.2507 · Cited by 1,863
Self-citationKim, S., Kim, D., Cho, S. W., Kim, J., & Kim, J.-S. (2014) · Genome Research · doi:10.1101/gr.171322.113 · Cited by 1,856
Self-citationMali, P., Aach, J., Stranges, P. B., Esvelt, K. M., Moosburner, M., Kosuri, S., Yang, L., & Church, G. M. (2013) · Nature Biotechnology · doi:10.1038/nbt.2675 · Cited by 1,752 · cited 3×
“Since we and others have reported RNA-guided genome editing in human cells in January, 2013 (Cho et al., 2013a; Cong et al., 2013; Jinek et al., 2013; Mali et al., 2013b), the CRISPRCas9 system has been widely used in many labs all around the world to modify genomes in various organisms and cells.”
BackgroundMethod
Cited by
Streptococcus thermophilus CRISPR-cas9 systems enable specific editing of the human genome
Müller, M., Lee, C. M., Gasiunas, G., Davis, T. H., Cradick, T. J., Siksnys, V., Bao, G., Cathomen, T., & Mussolino, C. (2016) · Molecular Therapy · doi:10.1038/mt.2015.218 · Cited by 254
Lau, C.-H., & Suh, Y. (2017) · F1000Research · doi:10.12688/f1000research.11243.1 · Cited by 161
Delivery of CRISPR/Cas9 for therapeutic genome editing
Xu, X., Wan, T., Xin, H., Li, D., Pan, H., Wu, J., & Ping, Y. (2019) · The Journal of Gene Medicine · doi:10.1002/jgm.3107 · Cited by 134
DIG-Seq: A genome-wide CRISPR off-target profiling method using chromatin DNA
Kim, D., & Kim, J.-S. (2018) · Genome Research · doi:10.1101/gr.236620.118 · Cited by 108
Self-citationEfficient genomic correction methods in human iPS cells using CRISPR–Cas9 system
Li, H. L., Gee, P., Ishida, K., & Hotta, A. (2016) · Methods · doi:10.1016/j.ymeth.2015.10.015 · Cited by 62
Metadata
- Authors
- Koo, T., Lee, J., & Kim, J.-S.
- Venue
- Molecules and Cells
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 38
- Issue
- 6
- Pages
- 475-481
- ISSN
- 0219-1032 (ISSN-L)
- 1016-8478
- OpenAlex
- W2274986902
- Cited by
- 207
- References
- 23
- FWCI
- 11.71
- Type
- journal article
- Language
- en
- Open access
- gold
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