ArticleNature communications2023
Simultaneous inhibition of DNA-PK and Polϴ improves integration efficiency and precision of genome editing.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- CRISPR for cystic fibrosis: Advances and insights from a systematic review.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Pooled it
- Interfering with DNA repair pathways to enhance CRISPR-Cas9-mediated homology-directed repair in a chelicerate genetic model.iScience · 2026Article
- Enhanced γ-globin reactivation and sickle cell correction through a repressor-to-activator motif switch in theMolecular therapy. Nucleic acids · 2026Article
- Recent Advances in CRISPR/Cas Technologies for Biological Discovery, Therapeutics, and Diagnostics.Biomolecules · 2026Review
- Article
- Donor-complementary prime editing enables precise kilobase and library-compatible DNA insertions.Nature biotechnology · 2026Article
- A PepFect14 analog improves non-viral CRISPR delivery in primary human cells to facilitate genome editing and repair.Bioengineering & translational medicine · 2026Article
- Apoptosis-driven chromosomal rearrangements in cancer: CAD cleavage, nuclear architecture, and microhomology-mediated end joining.Oncogenesis · 2026Review
- In vivo systematic detection of the outcomes of CRISPR-Cas9-mediated DNA repair in skeletal muscle stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- CRISPR/Cas9-Based Genome Editing: Understanding Differences in DNA Repair Pathways, Profiles, and Outcomes.International journal of molecular sciences · 2026Review
- Prime editing-mediated microhomology enables efficient replacement of large DNA.Nucleic acids research · 2026Article
- Modeling and correction of SCID-X1 using CRISPR-Cas9 homology-directed repair in human HSPCs.Molecular therapy. Nucleic acids · 2026Article
- Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Article
- Harnessing Deep Learning Models for Guide RNA Optimization and Off-Target Prediction in CRISPR Systems.Biotechnology journal · 2026Review
- Simultaneous orthogonal cell engineering by a single CRISPR-Cas9 polyfunctional editor.Nature communications · 2026Article
- A mutational scar-based genome-wide map of DNA double-strand break repair.Nature communications · 2026Article
- Application of extracellular vesicles in the CRISPR-based diagnosis and treatment: possibilities and challenges.Journal of biological engineering · 2026Review
- DNA-PKcs inhibitor AZD7648 reveals sgRNA cross-contaminants and enhanced sensitivity of genome engineering off-target activity in HSPCs.Nucleic acids research · 2026Article
- Viral genome editing methods and applications in the CRISPR era.Journal of virology · 2026Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 5 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome editing, specifically CRISPR/Cas9 technology, has revolutionized biomedical research and offers potential cures for genetic diseases. Despite rapid progress, low efficiency of targeted DNA integration and generation of unintended mutations represent major limitations for genome editing applications caused by the interplay with DNA double-strand break repair pathways. To address this, we conduct a large-scale compound library screen to identify targets for enhancing targeted genome insertions. Our study reveals DNA-dependent protein kinase (DNA-PK) as the most effective target to improve CRISPR/Cas9-mediated insertions, confirming previous findings. We extensively characterize AZD7648, a selective DNA-PK inhibitor, and find it to significantly enhance precise gene editing. We further improve integration efficiency and precision by inhibiting DNA polymerase theta (Polϴ). The combined treatment, named 2iHDR, boosts templated insertions to 80% efficiency with minimal unintended insertions and deletions. Notably, 2iHDR also reduces off-target effects of Cas9, greatly enhancing the fidelity and performance of CRISPR/Cas9 gene editing.
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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.