ArticleNature biotechnology2022
Fludarabine increases nuclease-free AAV- and CRISPR/Cas9-mediated homologous recombination in mice.
Article in Nature biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Real-Time Feedback Strategically Regulates Optoelectronics for Customized Optogenetic Spinal Cord Regeneration.Exploration (Beijing, China) · 2026Article
- Targeting phenol-soluble modulin α3-driven M1 macrophage polarization and necroptosis mitigates MRSA infection in mice.Nature communications · 2026Article
- Genome engineering with Cas9 and AAV repair templates, successes and pitfalls.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Clofarabine Enhances the Transduction Efficiency of Recombinant AAV2 in the Retina.Investigative ophthalmology & visual science · 2025Article
- AAV-mediated genome editing is influenced by the formation of R-loops.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- R-loops facilitate AAV-mediated nuclease-free gene targeting.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Gene Therapy for Inherited Liver Disease: To Add or to Edit.International journal of molecular sciences · 2024Review
- AAV-mediated genome editing is influenced by the formation of R-loops.bioRxiv : the preprint server for biology · 2024Article
- Review
- CRISPR-Cas9-mediated somatic correction of a one-base deletion in the Ugt1a gene ameliorates hyperbilirubinemia in Crigler-Najjar syndrome mice.Molecular therapy. Methods & clinical development · 2023Article
- Lethality rescue and long-term amelioration of a citrullinemia type I mouse model by neonatal gene-targeting combined to SaCRISPR-Cas9.Molecular therapy. Methods & clinical development · 2023Article
- A promoterless AAV6.2FF-based lung gene editing platform for the correction of surfactant protein B deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Genome editing without nucleases confers proliferative advantage to edited hepatocytes and corrects Wilson disease.JCI insight · 2023Article
- [Observation of liver indexes in patients with relapsed/refractory multiple myeloma treated with CAR-T-cells based on BCMA].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2023Article
- Promoterless Gene Targeting Approach Combined to CRISPR/Cas9 Efficiently Corrects Hemophilia B Phenotype in Neonatal Mice.Frontiers in genome editing · 2022Article
- CRISPR/Cas systems: Delivery and application in gene therapy.Frontiers in bioengineering and biotechnology · 2022Review
- Growth advantage of corrected hepatocytes in a juvenile model of methylmalonic acidemia following liver directed adeno-associated viral mediated nuclease-free genome editing.Molecular genetics and metabolismArticle
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Homologous recombination (HR)-based gene therapy using adeno-associated viruses (AAV-HR) without nucleases has several advantages over classic gene therapy, especially the potential for permanent transgene expression. However, the low efficiency of AAV-HR remains a major limitation. Here, we tested a series of small-molecule compounds and found that ribonucleotide reductase (RNR) inhibitors substantially enhance AAV-HR efficiency in mouse and human liver cell lines approximately threefold. Short-term administration of the RNR inhibitor fludarabine increased the in vivo efficiency of both non-nuclease- and CRISPR/Cas9-mediated AAV-HR two- to sevenfold in the murine liver, without causing overt toxicity. Fludarabine administration induced transient DNA damage signaling in both proliferating and quiescent hepatocytes. Notably, the majority of AAV-HR events occurred in non-proliferating hepatocytes in both fludarabine-treated and control mice, suggesting that the induction of transient DNA repair signaling in non-dividing hepatocytes was responsible for enhancing AAV-HR efficiency in mice. These results suggest that use of a clinically approved RNR inhibitor can potentiate AAV-HR-based genome-editing therapeutics.
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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.