ArticleNucleic acids research2012
Chromosomal context and epigenetic mechanisms control the efficacy of genome editing by rare-cutting designer endonucleases.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 70 citations in OpenAlex.
- Precision gene editing: The power of CRISPR-Cas in modern genetics.Molecular therapy. Nucleic acids · 2025Review
- Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.Journal of hematology & oncology · 2025Review
- Developing a universal multi-epitope protein vaccine candidate for enhanced borna virus pandemic preparedness.Frontiers in immunology · 2024Article
- Protocol to measure end resection intermediates at sequence-specific DNA double-strand breaks by quantitative polymerase chain reaction using ER-AsiSI U2OS cells.STAR protocols · 2022Article
- Identification of Loci Enabling Stable and High-Level Heterologous Gene Expression.Frontiers in bioengineering and biotechnology · 2021Article
- Targeted gene therapy into a safe harbor site in human hematopoietic progenitor cells.Gene therapy · 2020Article
- New Human Chromosomal Sites with "Safe Harbor" Potential for Targeted Transgene Insertion.Human gene therapy · 2019Article
- The Chromatin Structure of CRISPR-Cas9 Target DNA Controls the Balance between Mutagenic and Homology-Directed Gene-Editing Events.Molecular therapy. Nucleic acids · 2019Article
- Biasing genome-editing events toward precise length deletions with an RNA-guided TevCas9 dual nuclease.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Engineering a Nickase on the Homing Endonuclease I-DmoI Scaffold.The Journal of biological chemistry · 2015Article
- Optimized tuning of TALEN specificity using non-conventional RVDs.Scientific reports · 2015Article
- Engineering of customized meganucleases via in vitro compartmentalization and in cellulo optimization.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Lentiviral protein delivery of meganucleases in human cells mediates gene targeting and alleviates toxicity.Gene therapy · 2014Article
- Exploring the transcription activator-like effectors scaffold versatility to expand the toolbox of designer nucleases.BMC molecular biology · 2014Article
- BuD, a helix-loop-helix DNA-binding domain for genome modification.Acta crystallographica. Section D, Biological crystallography · 2014Article
- Efficient design of meganucleases using a machine learning approach.BMC bioinformatics · 2014Article
- Quantifying genome-editing outcomes at endogenous loci with SMRT sequencing.Cell reports · 2014Article
- Comprehensive analysis of the specificity of transcription activator-like effector nucleases.Nucleic acids research · 2014Article
- Redesign of extensive protein-DNA interfaces of meganucleases using iterative cycles of in vitro compartmentalization.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
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Corrections and comments
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Authors and funding
31 authors at 8 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability to specifically engineer the genome of living cells at precise locations using rare-cutting designer endonucleases has broad implications for biotechnology and medicine, particularly for functional genomics, transgenics and gene therapy. However, the potential impact of chromosomal context and epigenetics on designer endonuclease-mediated genome editing is poorly understood. To address this question, we conducted a comprehensive analysis on the efficacy of 37 endonucleases derived from the quintessential I-CreI meganuclease that were specifically designed to cleave 39 different genomic targets. The analysis revealed that the efficiency of targeted mutagenesis at a given chromosomal locus is predictive of that of homologous gene targeting. Consequently, a strong genome-wide correlation was apparent between the efficiency of targeted mutagenesis (≤ 0.1% to ≈ 6%) with that of homologous gene targeting (≤ 0.1% to ≈ 15%). In contrast, the efficiency of targeted mutagenesis or homologous gene targeting at a given chromosomal locus does not correlate with the activity of individual endonucleases on transiently transfected substrates. Finally, we demonstrate that chromatin accessibility modulates the efficacy of rare-cutting endonucleases, accounting for strong position effects. Thus, chromosomal context and epigenetic mechanisms may play a major role in the efficiency rare-cutting endonuclease-induced genome engineering.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.