ArticleGenome medicine2015
Pharmacological inhibition of DNA-PK stimulates Cas9-mediated genome editing.
Article in Genome medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
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Who cites it
160 citing papers in PubMed, 268 citations in OpenAlex.
- CRISPR/Cas9-based repair of a heterozygous HNF1A mutation in patient-derived hiPSCs.Human genetics · 2026Article
- CRISPR/Cas system as a novel therapeutic strategy to combat multi-drug-resistant bacteria.Archives of microbiology · 2026Review
- CRISPR Gene Tagging for Illuminating Endogenous Protein Dynamics.International journal of molecular sciences · 2026Review
- Single-cell multiplex approaches deeply map ON-target CRISPR-genotoxicity and reveal its mitigation by palbociclib and long-term engraftment.Nature communications · 2026Article
- Review
- Efficient high-precision transgene knock-in by Recombinases (Redα/β)-enhanced DNA integration-CRISPR-Cas9 (RED-CRISPR).Nature communications · 2025Article
- 53BP1-RIF1 and DNA-PKcs show distinct genetic interactions with diverse chromosomal break repair outcomes.Nature communications · 2025Article
- Precision T cell correction platform for inborn errors of immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations.Nature biotechnology · 2025Article
- Optimizing CRISPR methodology for precise gene editing in the erythroid cell line BEL-A with high efficiency generation of a sickle cell anemia model.Haematologica · 2025Article
- Improving Gene Knock-In Efficiencies in Sheep Primary Cells Using a CRISPR/Cas9-Gal4 System.Current issues in molecular biology · 2025Article
- Off-target effects in CRISPR-Cas genome editing for human therapeutics: Progress and challenges.Molecular therapy. Nucleic acids · 2025Review
- ONE-STEP tagging: a versatile method for rapid site-specific integration by simultaneous reagent delivery.Nucleic acids research · 2025Article
- Gene editing in hematopoietic stem cells by co-delivery of Cas9/sgRNA ribonucleoprotein and templates for homology-directed repair in 'all-in-one' lentivirus-derived nanoparticles.Nucleic acids research · 2025Article
- Refined DNA repair manipulation enables a universal knock-in strategy in mouse embryos.Nature communications · 2025Article
- Enhancing Specificity, Precision, Accessibility, Flexibility, and Safety to Overcome Traditional CRISPR/Cas Editing Challenges and Shape Future Innovations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- CRISPR/Cas9 Ribonucleoprotein Delivery Enhanced by Lipo-Xenopeptide Carriers and Homology-Directed Repair Modulators: Insights from Reporter Cell Lines.International journal of molecular sciences · 2025Article
- Weaponizing CRISPR/Cas9 for selective elimination of cells with an aberrant genome.DNA repair · 2025Article
- Autophagy induction enhances homologous recombination-associated CRISPR-Cas9 gene editing.Nucleic acids research · 2025Article
- Review
100 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe ability to modify the genome of any cell at a precise location has drastically improved with the recent discovery and implementation of CRISPR/Cas9 editing technology. However, the capacity to introduce specific directed changes at given loci is hampered by the fact that the major cellular repair pathway that occurs following Cas9-mediated DNA cleavage is the erroneous non-homologous end joining (NHEJ) pathway. Homology-directed recombination (HDR) is far less efficient than NHEJ and makes screening of clones containing directed changes time-consuming and labor-intensive.
methodsWe investigated the possibility of pharmacologically inhibiting DNA-PKcs, a key player in NHEJ, using small molecule inhibitors (NU7441 and KU-0060648), to ameliorate the rates of HDR repair events. These compounds were tested in a sensitive reporter assay capable of simultaneously informing on NHEJ and HDR, as well as on an endogenous gene targeted by Cas9.
resultsWe find that NU7441 and KU-0060648 reduce the frequency of NHEJ while increasing the rate of HDR following Cas9-mediated DNA cleavage.
conclusionsOur results identify two small molecules compatible for use with Cas9-editing technology to improve the frequency of HDR.
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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.