ArticleNucleic acids research2023
A novel Cas9 fusion protein promotes targeted genome editing with reduced mutational burden in primary human cells.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Chromatin Modifications Orchestrate DNA Repair Pathway Choice: Epigenetics Strategies for Enhancing CRISPR-Cas9-Mediated Knock-In Efficiency.Cell proliferation · 2026Review
- Discovery and engineering of retrons for precise genome editing.Nature biotechnology · 2026Article
- CRISPR-cas systems in pharmacology: functional pharmacogenomics, drug screening, resistance, and therapeutic translation.Functional & integrative genomics · 2026Review
- Genotoxicity profiling reveals distinct platform-and cell type-specific effects in therapeutic gene editing for genetic hyperinflammation.Cell stem cell · 2026Article
- Parallel Activation and Interference CRISPR (PAIR) with Sequencing Uncovers DNA Repair Networks Guiding Precision Cell Engineering.bioRxiv : the preprint server for biology · 2026Article
- Orthogonal CRISPR systems for targeted integration and multiplex base editing enable nonviral engineering of allogeneic CAR-T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Review
- Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations.Nature biotechnology · 2025Article
- Off-target effects in CRISPR-Cas genome editing for human therapeutics: Progress and challenges.Molecular therapy. Nucleic acids · 2025Review
- The hidden risks of CRISPR/Cas: structural variations and genome integrity.Nature communications · 2025Review
- DNA large fragment deleting by compact, sequence-motif-free and specific TaqTth-hpRNA assisted with the microhomology-mediated end joining pathway.Nucleic acids research · 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
- Fine-Tuning Homology-Directed Repair (HDR) for Precision Genome Editing: Current Strategies and Future Directions.International journal of molecular sciences · 2025Review
- Multiplex engineering and multifunction T cells for precise and effective immunotherapies.Frontiers in immunology · 2025Review
- Current Non-Viral-Based Strategies to Manufacture CAR-T Cells.International journal of molecular sciences · 2024Review
- CRISPR-Cas9-mediated homology-directed repair for precise gene editing.Molecular therapy. Nucleic acids · 2024Review
- Accelerating Diverse Cell-Based Therapies Through Scalable Design.Annual review of chemical and biomolecular engineering · 2024Review
- Non-viral DNA delivery and TALEN editing correct the sickle cell mutation in hematopoietic stem cells.Nature communications · 2024Article
- Developmental progression of DNA double-strand break repair deciphered by a single-allele resolution mutation classifier.Nature communications · 2024Article
- Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Precise genome editing requires the resolution of nuclease-induced DNA double strand breaks (DSBs) via the homology-directed repair (HDR) pathway. In mammals, this is typically outcompeted by non-homologous end-joining (NHEJ) that can generate potentially genotoxic insertion/deletion mutations at DSB sites. Because of higher efficacy, clinical genome editing has been restricted to imperfect but efficient NHEJ-based approaches. Hence, strategies that promote DSB resolution via HDR are essential to facilitate clinical transition of HDR-based editing strategies and increase safety. Here we describe a novel platform that consists of a Cas9 fused to DNA repair factors to synergistically inhibit NHEJ and favor HDR for precise repairing of Cas-induced DSBs. Compared to canonical CRISPR/Cas9, the increase in error-free editing ranges from 1.5-fold to 7-fold in multiple cell lines and in primary human cells. This novel CRISPR/Cas9 platform accepts clinically relevant repair templates, such as oligodeoxynucleotides (ODNs) and adeno-associated virus (AAV)-based vectors, and has a lower propensity to induce chromosomal translocations as compared to benchmark CRISPR/Cas9. The observed reduced mutational burden, resulting from diminished indel formation at on- and off-target sites, provides a remarkable gain in safety and advocates this novel CRISPR system as an attractive tool for therapeutic applications depending on precision genome 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.