The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Genome Engineering with Targetable Nucleases
Abstract
Current technology enables the production of highly specific genome modifications with excellent efficiency and specificity. Key to this capability are targetable DNA cleavage reagents and cellular DNA repair pathways. The break made by these reagents can produce localized sequence changes through inaccurate nonhomologous end joining (NHEJ), often leading to gene inactivation. Alternatively, user-provided DNA can be used as a template for repair by homologous recombination (HR), leading to the introduction of desired sequence changes. This review describes three classes of targetable cleavage reagents: zinc-finger nucleases (ZFNs), transcription activator–like effector nucleases (TALENs), and CRISPR/Cas RNA-guided nucleases (RGNs). As a group, these reagents have been successfully used to modify genomic sequences in a wide variety of cells and organisms, including humans. This review discusses the properties, advantages, and limitations of each system, as well as the specific considerations required for their use in different biological systems.
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“Genome-editing technologies may offer a powerful approach to treat many human diseases, including HIV/AIDS, haemophilia, sickle-cell anaemia and several forms of cancer 3 .”
From Don’t edit the human germ line (2015) · cites this paper as [3]
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
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., & Mello, C. C. (1998) · Nature · doi:10.1038/35888 · Cited by 15,429
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
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
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
CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes
Gilbert, L. A., Larson, M. H., Morsut, L., Liu, Z., Brar, G. A., Torres, S. E., Stern-Ginossar, N., Brandman, O., Whitehead, E. H., Doudna, J. A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.044 · Cited by 3,696 · cited 1×
“A nuclease-dead version of the Cas9 protein, when linked to such a domain, becomes an RNA-guided TF (109, 110).”
BackgroundWang, H., Yang, H., Shivalila, C. S., Dawlaty, M. M., Cheng, A. W., Zhang, F., & Jaenisch, R. (2013) · Cell · doi:10.1016/j.cell.2013.04.025 · Cited by 3,495
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
Research works printed but not linked: 254
- 10.1038/317230a0 · DOI
- 10.1016/0092-8674(86)90463-0 · DOI
- 10.1038/336348a0 · DOI · Paper page
- 10.1016/0076-6879(83)01015-0 · DOI
- 10.1073/pnas.76.10.4951 · DOI
- 10.1126/science.288.5473.2013 · DOI
- 10.1146/annurev.ge.15.120181.000303 · DOI
- 10.1242/jcs.074427 · DOI
- 10.1534/genetics.111.134577 · DOI
- 10.1128/MCB.15.4.1968 · DOI
- Plessis A, 1992, Genetics, 130, 451, 10.1093/genetics/130.3.451 · DOI
- 10.1128/MCB.14.12.8096 · DOI
- Rudin N, 1989, Genetics, 122, 519, 10.1093/genetics/122.3.519 · DOI
- 10.1016/j.molcel.2012.07.029 · DOI
- 10.1002/mc.20501 · DOI
- 10.1021/ja0621795 · DOI
- 10.1021/bi051379a · DOI
- 10.1534/genetics.111.131433 · DOI · Paper page
- 10.1073/pnas.93.3.1156 · DOI · Paper page
- 10.1038/mt.2012.171 · DOI
- 10.1016/j.tibtech.2013.04.004 · DOI · Paper page
- 10.1093/nar/gkr242 · DOI
- 10.1073/pnas.1107719108 · DOI
- 10.1016/j.str.2010.12.003 · DOI
- 10.1073/pnas.89.10.4275 · DOI
- 10.1073/pnas.91.3.883 · DOI
- 10.1002/j.1460-2075.1985.tb03825.x · DOI
- 10.1073/pnas.85.1.99 · DOI
- 10.1126/science.2028256 · DOI
- 10.1146/annurev.biochem.70.1.313 · DOI
- 10.1073/pnas.89.16.7345 · DOI
- 10.1073/pnas.90.6.2256 · DOI
- 10.1073/pnas.91.23.11163 · DOI
- 10.1073/pnas.91.23.11168 · DOI
- 10.1126/science.275.5300.657 · DOI
- 10.1073/pnas.96.6.2758 · DOI · Paper page
- 10.1074/jbc.M102604200 · DOI
- 10.1074/jbc.M506654200 · DOI
- 10.1074/jbc.M110669200 · DOI
- 10.1101/gr.089417.108 · DOI · Paper page
- 10.1101/gr.143693.112 · DOI
- 10.1038/nprot.2006.231 · DOI
- 10.1038/nprot.2010.34 · DOI
- 10.1038/nmeth0210-91a · DOI
- 10.1021/bi026806o · DOI
- 10.1038/nmeth0508-374 · DOI
- 10.1093/nar/gkm385 · DOI
- 10.1016/j.molcel.2008.06.016 · DOI
- 10.1038/nmeth.1994 · DOI
- 10.1038/nmeth.1542 · DOI
- 10.1093/nar/gks1357 · DOI
- 10.1021/bi200393g · DOI
- 10.1073/pnas.98.4.1437 · DOI
- 10.1073/pnas.98.4.1432 · DOI
- 10.1021/ja00012a021 · DOI
- 10.1093/nar/28.17.3361 · DOI
- 10.1073/pnas.95.18.10570 · DOI
- 10.1016/j.jmb.2010.04.060 · DOI · Paper page
- 10.1128/MCB.21.1.289-297.2001 · DOI
- 10.1038/mt.2008.233 · DOI
- 10.1016/j.bmcl.2009.02.109 · DOI
- 10.1038/nature03556 · DOI
- 10.1126/science.1204094 · DOI · Paper page
- 10.1126/science.1178811 · DOI · Paper page
- 10.1126/science.1178817 · DOI
- 10.1126/science.1215670 · DOI
- 10.1126/science.1216211 · DOI
- 10.1371/journal.pone.0045383 · DOI
- 10.1038/ncomms1962 · DOI
- 10.1038/nbt.2304 · DOI
- 10.1093/nar/gkt085 · DOI
- 10.1074/jbc.C112.408864 · DOI
- 10.1093/nar/gks624 · DOI
- 10.1093/nar/gkr218 · DOI
- 10.1038/nbt.1939 · DOI
- 10.1093/nar/gkr151 · DOI
- 10.1186/1471-2105-14-1 · DOI
- Reyon D, 2012, Curr. Protoc. Mol. Biol., 12, 12.15
- 10.1038/nbt.2170 · DOI
- 10.1111/gtc.12037 · DOI
- 10.1038/nprot.2011.431 · DOI
- 10.1038/nbt.2460 · DOI
- 10.1186/1480-9222-15-3 · DOI
- 10.1002/anie.201203597 · DOI
- 10.1371/journal.pone.0019722 · DOI
- 10.1534/genetics.110.120717 · DOI · Paper page
- 10.1093/nar/gkq704 · DOI
- 10.1038/nbt.1755 · DOI · Paper page
- 10.1046/j.1365-2958.2002.02839.x · DOI · Paper page
- 10.1038/nbt.2507 · DOI · Paper page
- 10.1101/gr.162339.113 · DOI · Paper page
- 10.1038/ncomms2782 · DOI
- 10.1073/pnas.1117984109 · DOI
- 10.1093/nar/gkr1112 · DOI
- 10.1093/nar/gkt080 · DOI
- 10.1124/mol.104.002758 · DOI
- 10.1093/nar/gkt071 · DOI
- 10.1093/nar/gks875 · DOI
- 10.1073/pnas.0535280100 · DOI
- 10.1126/science.1079512 · DOI
- 10.1038/nbt1409 · DOI
- 10.1038/nbt1398 · DOI
- 10.1534/genetics.110.117002 · DOI
- 10.1073/pnas.1211446109 · DOI
- 10.1038/nbt.1731 · DOI
- 10.1126/science.1172447 · DOI · Paper page
- 10.1073/pnas.1106422108 · DOI
- 10.1073/pnas.1009424107 · DOI
- 10.1073/pnas.0810475105 · DOI
- 10.1038/nature11537 · DOI
- 10.1371/journal.pone.0068708 · DOI
- 10.1038/nmeth.2374 · DOI
- 10.1073/pnas.0605633103 · DOI
- 10.1534/genetics.113.155382 · DOI
- 10.1126/science.1207773 · DOI
- 10.1093/nar/gks1356 · DOI
- 10.1534/genetics.113.155879 · DOI
- 10.1038/nmeth.2641 · DOI
- 10.1534/genetics.113.155754 · DOI · Paper page
- 10.1534/genetics.113.156075 · DOI
- 10.1534/genetics.113.156299 · DOI
- 10.1534/genetics.113.155853 · DOI
- 10.1038/nbt1319 · DOI · Paper page
- 10.2144/04364PF01 · DOI
- 10.1371/journal.pgen.1002861 · DOI
- 10.1534/g3.113.007260 · DOI
- 10.1038/nmeth.2364 · DOI
- 10.1371/journal.pone.0053217 · DOI
- 10.1038/srep01253 · DOI
- 10.1093/nar/gkq379 · DOI
- 10.1534/genetics.109.101329 · DOI
- 10.1101/gr.099747.109 · DOI
- 10.1101/gr.154070.112 · DOI
- 10.1101/gr.129635.111 · DOI
- 10.1073/pnas.0902076106 · DOI · Paper page
- 10.1101/gr.147314.112 · DOI
- 10.1038/nmeth.1653 · DOI
- 10.1101/gr.138792.112 · DOI
- 10.1073/pnas.0810588106 · DOI
- 10.1093/nar/gks179 · DOI
- 10.1101/gr.122879.111 · DOI
- 10.1038/nmeth.1648 · DOI
- 10.1534/g3.112.005439 · DOI
- 10.1128/MCB.18.1.93 · DOI
- 10.1534/genetics.105.052829 · DOI
- 10.1038/nbt1317 · DOI · Paper page
- 10.1093/nar/gkq787 · DOI
- 10.1038/nrg2842 · DOI · Paper page
- 10.1038/nmeth.1670 · DOI · Paper page
- 10.1038/nbt.1948 · DOI · Paper page
- 10.1016/j.stem.2012.11.011 · DOI
- 10.1242/bio.20133871 · DOI
- 10.1093/nar/gkr597 · DOI · Paper page
- 10.1038/mt.2013.111 · DOI
- 10.1093/nar/gkt714 · DOI · Paper page
- 10.1038/nbt.2684 · DOI
- 10.1016/j.cell.2013.08.021 · DOI · Paper page
- 10.1093/nar/gkt638 · DOI
- 10.1016/j.jgg.2012.04.003 · DOI
- 10.1016/j.celrep.2013.06.020 · DOI
- 10.1534/genetics.113.152710 · DOI
- 10.1534/genetics.113.153825 · DOI
- 10.1038/nbt.1934 · DOI
- 10.1093/nar/gks518 · DOI
- 10.1093/nar/gks1356 · DOI
- 10.1371/journal.pone.0037877 · DOI
- 10.1038/cr.2013.45 · DOI
- 10.1371/journal.pone.0068708 · DOI
- 10.1093/nar/gks1144 · DOI
- 10.1073/pnas.1308335110 · DOI · Paper page
- 10.1073/pnas.0409339102 · DOI
- 10.1073/pnas.1000234107 · DOI
- 10.1073/pnas.0914991107 · DOI
- 10.1093/nar/gkt780 · DOI
- 10.1038/nrg1619 · DOI
- 10.1038/nbt.1940 · DOI
- 10.1093/nar/gkt258 · DOI
- 10.1038/cr.2013.46 · DOI · Paper page
- 10.1073/pnas.1218721110 · DOI
- Wang H, 2013, Cell Rep., 153, 910
- 10.1101/gr.145599.112 · DOI
- 10.1093/nar/gkt135 · DOI · Paper page
- 10.1038/nature07845 · DOI
- 10.1104/pp.112.205179 · DOI
- 10.1038/nature07992 · DOI
- 10.1104/pp.110.164806 · DOI
- 10.1016/B978-0-12-404742-6.00002-8 · DOI
- 10.1038/cr.2011.153 · DOI
- 10.1371/journal.pone.0045035 · DOI
- 10.1016/j.ibmb.2012.10.011 · DOI
- 10.1016/j.ibmb.2010.07.012 · DOI
- 10.1038/cr.2013.146 · DOI
- 10.1002/adfm.201300365 · DOI
- 10.1371/journal.pone.0060082 · DOI
- 10.1371/journal.pone.0074511 · DOI
- 10.1126/science.1246981 · DOI · Paper page
- 10.1038/nmeth.1674 · DOI
- 10.1101/gr.122358.111 · DOI
- 10.1371/journal.pone.0063074 · DOI
- 10.1002/bit.24892 · DOI
200 of 254 shown
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Dunbar, C. E., High, K. A., Joung, J. K., Kohn, D. B., Ozawa, K., & Sadelain, M. (2018) · Science · doi:10.1126/science.aan4672 · Cited by 1,410
Optimized CRISPR/Cas tools for efficient germline and somatic genome engineering in Drosophila
Port, F., Chen, H.-M., Lee, T., & Bullock, S. L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405500111 · Cited by 1,046
A CRISPR/Cas9 Toolbox for Multiplexed Plant Genome Editing and Transcriptional Regulation
Lowder, L. G., Zhang, D., Baltes, N. J., Paul, J. W., Tang, X., Zheng, X., Voytas, D. F., Hsieh, T.-F., Zhang, Y., & Qi, Y. (2015) · Plant Physiology · doi:10.1104/pp.15.00636 · Cited by 707
Induced Pluripotent Stem Cells Meet Genome Editing
Hockemeyer, D., & Jaenisch, R. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.04.013 · Cited by 499
“The low frequency of spontaneous homology mediated gene targeting in hPSCs was dramatically increased through the development of site-specific nucleases (SSN) as a tool for their genetic engineering (reviewed in (Carroll, 2014; Hsu et al., 2014; Urnov et al., 2010)).”
MethodDon’t edit the human germ line
Lanphier, E., Urnov, F., Haecker, S. E., Werner, M., & Smolenski, J. (2015) · Nature · doi:10.1038/519410a · Cited by 530
Metadata
- Authors
- Carroll, D.
- Affiliations
- University of Utah (US)
- Corresponding author
- Carroll, Dana
- ORCID
- Carroll, Dana
- Venue
- Annual Review of Biochemistry
- Publisher
- Annual Reviews
- Published
- 2014-06-02
- Volume
- 83
- Issue
- 1
- Pages
- 409-439
- ISSN
- 0066-4154 (ISSN-L)
- 1545-4509
- OpenAlex
- W2123366092
- Cited by
- 568
- References
- 34
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 46 · 2023: 33 · 2022: 35 · 2021: 45 · 2020: 40 · 2019: 43 · 2018: 52 · 2017: 60 · 2016: 64 · 2015: 77 · 2014: 27
- FWCI
- 6.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM078571)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- genome editing, zinc finger nucleases, TALEN, CRISPR-Cas, RNA-guided nucleases, DNA repair, non-homologous end joining, homologous recombination, gene inactivation
- MeSH terms
- Animals, DNA, DNA Damage, DNA Repair, Drosophila, Drosophila melanogaster, Endonucleases, Genetic Engineering, Humans, Recombination, Genetic, Zebrafish, Protein Engineering, Zinc Fingers, Genome, Gene Deletion, Arabidopsis, Protein Structure, Tertiary, Genomics, Mice, Rats, DNA End-Joining Repair
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