The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining
Open accessAbstract
Methods to introduce targeted double-strand breaks (DSBs) into DNA enable precise genome editing by increasing the rate at which externally supplied DNA fragments are incorporated into the genome through homologous recombination. The efficiency of these methods is limited by nonhomologous end joining (NHEJ), an alternative DNA repair pathway that competes with homology-directed repair (HDR). To promote HDR at the expense of NHEJ, we targeted DNA ligase IV, a key enzyme in the NHEJ pathway, using the inhibitor Scr7. Scr7 treatment increased the efficiency of HDR-mediated genome editing, using Cas9 in mammalian cell lines and in mice for all four genes examined, up to 19-fold. This approach should be applicable to other customizable endonucleases, such as zinc finger nucleases and transcription activator-like effector nucleases, and to nonmammalian cells with sufficiently conserved mechanisms of NHEJ and HDR.
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 says what the claim attributes to it.
In the citing paper
“Even in the presence of donor template DNA, NHEJ is the more frequent repair mechanism observed from CRISPR/Cas9 editing (Maruyama et al., 2015).”
From Delivering CRISPR: a review of the challenges and approaches (2018) · cites this paper as Maruyama et al., 2015
The cited source says what the claim attributes to it.
In the citing paper
“or inhibiting the NHEJ pathway [113] have shown to be useful as means of increasing the efficiency of HDR after Cas9 cleavage.”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [113]
In the citing paper
“Although inhibiting the NHEJ pathway with gene silencing or chemical inhibitors can partially increase the efficiency of HDR pathway, the gene repair efficacy still needs to be further improved for disease therapy [82, 85].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [85]
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
Robinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390
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
Wang, 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
CRISPR-Cas systems for editing, regulating and targeting genomes
Sander, J. D., & Joung, J. K. (2014) · Nature Biotechnology · doi:10.1038/nbt.2842 · Cited by 3,153
Genetic screens in human cells using the CRISPR-Cas9 system
Wang, T., Wei, J. J., Sabatini, D. M., & Lander, E. S. (2014) · Science · doi:10.1126/science.1246981 · Cited by 2,856
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
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
Yang, H., Wang, H., Shivalila, C. S., Cheng, A. W., Shi, L., & Jaenisch, R. (2013) · Cell · doi:10.1016/j.cell.2013.08.022 · Cited by 1,596
Double-strand break repair: 53BP1 comes into focus
Panier, S., & Boulton, S. J. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3719 · Cited by 1,168
Kamentsky, L. D., Jones, T. R., Fraser, A. N., Bray, M., Logan, D. J., Madden, K. L., Ljosa, V., Rueden, C., Eliceiri, K. W., & Carpenter, A. E. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr095 · Cited by 1,002
Cited by
Sorted by citations
Search-and-replace genome editing without double-strand breaks or donor DNA
Anzalone, A. V., Randolph, P. B., Davis, J. R., Sousa, A. A., Koblan, L. W., Levy, J. M., Chen, P. J., Wilson, C., Newby, G. A., Raguram, A., et al. (2019) · Nature · doi:10.1038/s41586-019-1711-4 · Cited by 4,767
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
Li, H., Yang, Y., Hong, W., Huang, M., Wu, M., & Zhao, X. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0089-y · Cited by 1,829
Off-target Effects in CRISPR/Cas9-mediated Genome Engineering
Zhang, X.-H., Tee, L. Y., Wang, X.-G., Huang, Q.-S., & Yang, S.-H. (2015) · Molecular Therapy - Nucleic Acids · doi:10.1038/mtna.2015.37 · Cited by 1,273
CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response
Haapaniemi, E., Botla, S., Persson, J., Schmierer, B., & Taipale, J. (2018) · Nature Medicine · doi:10.1038/s41591-018-0049-z · Cited by 1,264
Metadata
- Authors
- Maruyama, T., Dougan, S. K., Truttmann, M. C., Bilate, A. M., Ingram, J. R., & Ploegh, H. L.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Ploegh, Hidde L
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2015-03-23
- Volume
- 33
- Issue
- 5
- Pages
- 538-542
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC4618510
- OpenAlex
- W2008147758
- Cited by
- 1,137
- References
- 32
- Citations by year
- 2026: 39 · 2025: 58 · 2024: 62 · 2023: 67 · 2022: 108 · 2021: 101 · 2020: 117 · 2019: 122 · 2018: 125 · 2017: 139 · 2016: 143 · 2015: 55
- FWCI
- 66.47
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-02-05)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- PMC
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI087879)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- CRISPR/Cas9, genome editing efficiency, non-homologous end joining, homology-directed repair, DNA ligase IV, DNA double-strand break repair, zinc finger nucleases, TALEN
- MeSH terms
- DNA Ligase ATP, Animals, Cell Line, DNA Repair, Genetic Engineering, DNA Ligases, Pyrimidines, Schiff Bases, Zinc Fingers, Genome, Mice, DNA Breaks, Double-Stranded, Homologous Recombination, DNA End-Joining Repair, CRISPR-Cas Systems
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
