The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering
Open accessAbstract
Mice carrying mutations in multiple genes are traditionally generated by sequential recombination in embryonic stem cells and/or time-consuming intercrossing of mice with a single mutation. The CRISPR/Cas system has been adapted as an efficient gene-targeting technology with the potential for multiplexed genome editing. We demonstrate that CRISPR/Cas-mediated gene editing allows the simultaneous disruption of five genes (Tet1, 2, 3, Sry, Uty--8 alleles) in mouse embryonic stem (ES) cells with high efficiency. Coinjection of Cas9 mRNA and single-guide RNAs (sgRNAs) targeting Tet1 and Tet2 into zygotes generated mice with biallelic mutations in both genes with an efficiency of 80%. Finally, we show that coinjection of Cas9 mRNA/sgRNAs with mutant oligos generated precise point mutations simultaneously in two target genes. Thus, the CRISPR/Cas system allows the one-step generation of animals carrying mutations in multiple genes, an approach that will greatly accelerate the in vivo study of functionally redundant genes and of epistatic gene interactions.
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“Soon, all sorts of cells and some multicellular organisms would be the object of CRISPR-mediated manipulation, such as human cell cultures, mice, plants, yeasts, and the list goes on [62,63,64,65].”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [63]
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“The need for specific proteins tailored for each gene also makes multiplex gene editing a strenuous task for ZFNs and TALENs, while with Cas9 systems multiple genes can be targeted simply by delivering multiple gRNAs to the cells [63,98].”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [63]
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“focused on the issue of human germline engineering, as the methods have already been demonstrated in mice (6) and monkeys (7).”
From A prudent path forward for genomic engineering and germline gene modification (2015) · cites this paper as [6]
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“However, the desired recombination efficacy often occurs infrequently, which presents enormous challenges for robust applications [61, 82–84].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [61]
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“Recently, the CRISPR/Cas system has been successfully applied to human cells19,20,21,22 and several model organisms for genome editing.23,24,25,26”
From The CRISPR/Cas9 system facilitates clearance of the intrahepatic HBV templates in vivo (2014) · cites this paper as [26]
In the citing paper
“DNA sequence recognition requires only a single 20-nt guide RNA and a protospacer adjacent motif, which enables one to rapidly engineer and test a large number of DNA cleavage sites (17)(18)(19)(20).”
From RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection (2014) · cites this paper as [17]
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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
Self-citationRNA-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
Efficient genome editing in zebrafish using a CRISPR-Cas system
Hwang, W. Y., Fu, Y., Reyon, D., Maeder, M. L., Tsai, S. Q., Sander, J. D., Peterson, R. T., Yeh, J.-R. J., & Joung, J. K. (2013) · Nature Biotechnology · doi:10.1038/nbt.2501 · Cited by 2,937
Gasiunas, G., Barrangou, R., Horvath, P., & Siksnys, V. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208507109 · Cited by 2,769
CRISPR/Cas, the Immune System of Bacteria and Archaea
Horvath, P., & Barrangou, R. (2010) · Science · doi:10.1126/science.1179555 · Cited by 2,471
RNA-guided editing of bacterial genomes using CRISPR-Cas systems
Jiang, W., Bikard, D., Cox, D., Zhang, F., & Marraffini, L. A. (2013) · Nature Biotechnology · doi:10.1038/nbt.2508 · Cited by 2,429
Self-citationGenome editing with engineered zinc finger nucleases
Urnov, F. D., Rebar, E. J., Holmes, M. C., Zhang, H. S., & Gregory, P. D. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2842 · Cited by 2,285
Targeted 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
RNA-guided genetic silencing systems in bacteria and archaea
Wiedenheft, B., Sternberg, S. H., & Doudna, J. A. (2012) · Nature · doi:10.1038/nature10886 · Cited by 1,851
Double-Strand Break End Resection and Repair Pathway Choice
Symington, L. S., & Gautier, J. (2011) · Annual Review of Genetics · doi:10.1146/annurev-genet-110410-132435 · Cited by 1,556
Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation
Moran-Crusio, K., Reavie, L., Shih, A., Abdel-Wahab, O., Ndiaye-Lobry, D., Lobry, C., Figueroa, M. E., Vasanthakumar, A., Patel, J., Zhao, X., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.06.001 · Cited by 1,339
The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes
Gu, T., Guo, F., Yang, H., Wu, H.-P., Xu, G., Liu, W., Xie, Z.-G., Shi, L., He, X., Jin, S., et al. (2011) · Nature · doi:10.1038/nature10443 · Cited by 1,144
Self-citationMMEJ repair of double-strand breaks (director’s cut): deleted sequences and alternative endings
McVey, M., & Lee, S. E. (2008) · Trends in Genetics · doi:10.1016/j.tig.2008.08.007 · Cited by 1,039
TAL effectors: customizable proteins for DNA targeting
Bogdanove, A. J., & Voytas, D. F. (2011) · Science · doi:10.1126/science.1204094 · Cited by 984
Knockout Rats via Embryo Microinjection of Zinc-Finger Nucleases
Geurts, A. M., Cost, G. J., Freyvert, Y., Zeitler, B., Miller, J. C., Choi, V. M., Jenkins, S. S., Wood, A., Cui, X., Meng, X., et al. (2009) · Science · doi:10.1126/science.1172447 · Cited by 934
Genome editing with RNA-guided Cas9 nuclease in Zebrafish embryos
Chang, N., Sun, C., Gao, L., Zhu, D., Xu, X., Zhu, X., Xiong, J., & Xi, J. (2013) · Cell Research · doi:10.1038/cr.2013.45 · Cited by 833
Soldner, F., Laganière, J., Cheng, A. W., Hockemeyer, D., Gao, Q., Alagappan, R., Khurana, V., Golbe, L. I., Myers, R. H., Lindquist, S., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.019 · Cited by 728
Self-citationGene targeting in mice: functional analysis of the mammalian genome for the twenty-first century
Capecchi, M. (2005) · Nature reviews genetics · doi:10.1038/nrg1619 · Cited by 723
Li, Z., Cai, X., Cai, C.-L., Wang, J., Zhang, W., Petersen, B. E., Yang, F.-C., & Xu, M. (2011) · Blood · doi:10.1182/blood-2010-12-325241 · Cited by 671
Knockout rats generated by embryo microinjection of TALENs
Tesson, L., Usal, C., Ménoret, S., Leung, E., Niles, B. J., Remy, S., Santiago, Y., Vincent, A. I., Meng, X., Zhang, L., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1940 · Cited by 585
Generation of gene-modified mice via Cas9/RNA-mediated gene targeting
Shen, B., Zhang, J., Wu, H., Wang, J., Ma, K., Li, Z., Zhang, X., Zhang, P., & Huang, X. (2013) · Cell Research · doi:10.1038/cr.2013.46 · Cited by 511
A Rapid and General Assay for Monitoring Endogenous Gene Modification
Guschin, D. Y., Waite, A. J., Katibah, G. E., Miller, J. C., Holmes, M. C., & Rebar, E. J. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-753-2_15 · Cited by 509
Dawlaty, M. M., Ganz, K., Powell, B. E., Hu, Y.-C., Markoulaki, S., Cheng, A. W., Gao, Q., Kim, J., Choi, S.-W., Page, D. C., et al. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.07.010 · Cited by 508
Self-citationHigh-frequency genome editing using ssDNA oligonucleotides with zinc-finger nucleases
Chen, F., Pruett‐Miller, S. M., Huang, Y., Gjoka, M., Duda, K., Taunton, J., Collingwood, T. N., Frödin, M., & Davis, G. D. (2011) · Nature Methods · doi:10.1038/nmeth.1653 · Cited by 475
Dawlaty, M. M., Breiling, A., Le, T. T., Raddatz, G., Barrasa, M. I., Cheng, A. W., Gao, Q., Powell, B. E., Li, Z., Xu, M., et al. (2013) · Developmental Cell · doi:10.1016/j.devcel.2012.12.015 · Cited by 450
Self-citationKnockout mice created by TALEN-mediated gene targeting
Sung, Y. H., Baek, I., Kim, D. H., Jeon, J., Lee, J., Lee, K., Jeong, D., Kim, J., & Lee, H. (2013) · Nature Biotechnology · doi:10.1038/nbt.2477 · Cited by 361
Targeted integration in rat and mouse embryos with zinc-finger nucleases
Cui, X., Ji, D., Fisher, D. A. C., Wu, Y., Briner, D. M., & Weinstein, E. J. (2010) · Nature Biotechnology · doi:10.1038/nbt.1731 · Cited by 315
Gene targeting by homologous recombination in mouse zygotes mediated by zinc-finger nucleases
Meyer, M., de Angelis, M. H., Wurst, W., & Kühn, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009424107 · Cited by 286
Targeted Genome Modification in Mice Using Zinc-Finger Nucleases
Carbery, I. D., Ji, D., Harrington, A. N., Brown, V. E., Weinstein, E. J., Liaw, L., & Cui, X. (2010) · Genetics · doi:10.1534/genetics.110.117002 · Cited by 274
Harnessing transposons for cancer gene discovery
Copeland, N. G., & Jenkins, N. A. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2916 · Cited by 155
Wefers, B., Meyer, M., Ortiz, O., de Angelis, M. H., Hansen, J., Wurst, W., & Kühn, R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218721110 · Cited by 147
Harnessing transposons for cancer gene discovery
Neal, Copeland, Nancy, N., & Jenkins (2007) · 南京医科大学学报：英文版 · Cited by 128
High-throughput insertional mutagenesis screens in mice to identify oncogenic networks
Kool, J., & Berns, A. J. M. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2647 · Cited by 125
Gene Targeting in Drosophila and Caenorhabditis elegans With Zinc-Finger Nucleases
Carroll, D., Beumer, K. J., Morton, J. J., Bozas, A., & Trautman, J. K. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-232-8_5 · Cited by 48
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Metadata
- Authors
- Wang, H., Yang, H., Shivalila, C. S., Dawlaty, M. M., Cheng, A. W., Zhang, F., & Jaenisch, R.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Broad Institute (US)
- Corresponding author
- Jaenisch, Rudolf
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 153
- Issue
- 4
- Pages
- 910-918
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3969854
- OpenAlex
- W2170039745
- Cited by
- 3,495
- References
- 35
- Citations by year
- 2026: 63 · 2025: 94 · 2024: 166 · 2023: 203 · 2022: 210 · 2021: 239 · 2020: 286 · 2019: 299 · 2018: 332 · 2017: 352 · 2016: 392 · 2015: 362 · 2014: 359 · 2013: 134
- FWCI
- 186.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- Damon Runyon Cancer Research Foundation
- National Institutes of Health (2r01ca084198-10)
- National Institute of Mental Health (DP1MH100706)
- National Cancer Institute (R01-CA084198)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R37HD045022)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- CRISPR/Cas genome editing, multiplexed genome editing, mouse mutagenesis, TET1, TET2, TET3, SRY, UTY, biallelic variants, single guide RNA, zygote injection, mouse embryonic stem cells
- MeSH terms
- Animals, Base Sequence, Female, Male, Mice, Inbred C57BL, Mice, Inbred DBA, Molecular Sequence Data, Gene Targeting, Mice, Embryonic Stem Cells, RNA, Small Untranslated
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