ArticleNature biotechnology2019
Enhancing gene editing specificity by attenuating DNA cleavage kinetics.
Article in Nature biotechnology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 61 citations in OpenAlex.
- Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease.Scientific reports · 2024Trial
- Writing Big in Plant Genomes: Advances, Challenges and Strategies for Targeted Large-Fragment DNA Insertion.Plant, cell & environment · 2026Review
- Emerging therapeutic strategies for mitochondrial DNA-related diseases.Cell reports. Medicine · 2026Review
- Strategies to eliminate native T cell receptors for adoptive T cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Zinc finger proteins (ZFPs) in health and disease.Molecular biomedicine · 2026Review
- Advances in gene therapy for mitochondrial genetic disorders: current status and clinical implementation challenges.Journal of translational medicine · 2025Review
- Review
- TALEN-Interceded Genome Editing in Plants: Unveiling New Frontiers in Secondary Metabolite Improvement and Genetic Diversity.Plants (Basel, Switzerland) · 2025Review
- Off-target effects in CRISPR-Cas genome editing for human therapeutics: Progress and challenges.Molecular therapy. Nucleic acids · 2025Review
- Improving resolution with single-cell detection of CRISPR off-target events.Molecular therapy. Methods & clinical development · 2025Article
- Insights into the Epigenetic Basis of Plant Salt Tolerance.International journal of molecular sciences · 2024Review
- Gene therapy for CNS disorders: modalities, delivery and translational challenges.Nature reviews. Neuroscience · 2024Review
- Exploring treatment options in cancer: Tumor treatment strategies.Signal transduction and targeted therapy · 2024Review
- Epigenetic control of multiple genes with a lentiviral vector encoding transcriptional repressors fused to compact zinc finger arrays.Molecular therapy. Methods & clinical development · 2024Article
- Compact zinc finger architecture utilizing toxin-derived cytidine deaminases for highly efficient base editing in human cells.Nature communications · 2024Article
- Production of therapeutic levels of human FIX-R338L by engineered B cells using GMP-compatible medium.Molecular therapy. Methods & clinical development · 2023Article
- A universal deep-learning model for zinc finger design enables transcription factor reprogramming.Nature biotechnology · 2023Article
- Mitochondrial Base Editing: Recent Advances towards Therapeutic Opportunities.International journal of molecular sciences · 2023Review
- Correcting inborn errors of immunity: From viral mediated gene addition to gene editing.Seminars in immunology · 2023Review
- In search of an ideal template for therapeutic genome editing: A review of current developments for structure optimization.Frontiers in genome editing · 2023Review
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Engineered nucleases have gained broad appeal for their ability to mediate highly efficient genome editing. However the specificity of these reagents remains a concern, especially for therapeutic applications, given the potential mutagenic consequences of off-target cleavage. Here we have developed an approach for improving the specificity of zinc finger nucleases (ZFNs) that engineers the FokI catalytic domain with the aim of slowing cleavage, which should selectively reduce activity at low-affinity off-target sites. For three ZFN pairs, we engineered single-residue substitutions in the FokI domain that preserved full on-target activity but showed a reduction in off-target indels of up to 3,000-fold. By combining this approach with substitutions that reduced the affinity of zinc fingers, we developed ZFNs specific for the TRAC locus that mediated 98% knockout in T cells with no detectable off-target activity at an assay background of ~0.01%. We anticipate that this approach, and the FokI variants we report, will enable routine generation of nucleases for gene editing with no detectable off-target activity.
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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.