ArticleMolecular therapy. Nucleic acids2019
Improved Double-Nicking Strategies for COL7A1-Editing by Homologous Recombination.
Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Developing CRISPR-Based Therapies for Epidermolysis Bullosa: A Comprehensive Review of Current Strategies.Drugs · 2026Review
- Gene therapy for genodermatoses at the crossroads of innovation and clinical translation.Frontiers in bioengineering and biotechnology · 2026Review
- Clinical and Allelic Heterogeneity in a Small Cohort of Patients with Inherited Epidermolysis Bullosa.International journal of molecular sciences · 2025Article
- Efficient Dual Cas9 Nickase Correction of a Prevalent PathogenicJID innovations : skin science from molecules to population health · 2025Article
- Enhanced HDR-mediated correction of heterozygousMolecular therapy. Nucleic acids · 2025Article
- Repurposing diacerein for the treatment of chronic wounds in recessive-dystrophic epidermolysis bullosa patients by modulating matrix metalloproteinase-9 expression.The Journal of dermatology · 2025Article
- Immunological control of skin development: from homeostasis to developmental pathologies.Frontiers in immunology · 2025Review
- Gene-edited cells: novel allogeneic gene/cell therapy for epidermolysis bullosa.Journal of applied genetics · 2024Review
- Twin Prime Editing Mediated Exon Skipping/Reinsertion for Restored Collagen VII Expression in Recessive Dystrophic Epidermolysis Bullosa.The Journal of investigative dermatology · 2024Article
- Highly efficient CRISPR/Cas9-mediated exon skipping for recessive dystrophic epidermolysis bullosa.Bioengineering & translational medicine · 2024Article
- On- and off-target effects of paired CRISPR-Cas nickase in primary human cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Emerging Gene Therapeutics for Epidermolysis Bullosa under Development.International journal of molecular sciences · 2024Review
- CRISPR-Cas9-based non-viral gene editing therapy for topical treatment of recessive dystrophic epidermolysis bullosa.Molecular therapy. Methods & clinical development · 2023Article
- High-efficiency and multilocus targeted integration in CHO cells using CRISPR-mediated donor nicking and DNA repair inhibitors.Biotechnology and bioengineering · 2023Article
- Precise homology-directed installation of large genomic edits in human cells with cleaving and nicking high-specificity Cas9 variants.Nucleic acids research · 2023Article
- A Novel Fluorescence-Based Screen of Gene Editing Molecules for Junctional Epidermolysis Bullosa.International journal of molecular sciences · 2023Article
- Challenges of Gene Editing Therapies for Genodermatoses.International journal of molecular sciences · 2023Review
- Preclinical model for phenotypic correction of dystrophic epidermolysis bullosa byMolecular therapy. Methods & clinical development · 2022Article
- Genetic Disorders of the Extracellular Matrix: From Cell and Gene Therapy to Future Applications in Regenerative Medicine.Annual review of genomics and human genetics · 2022Review
- Paired nicking-mediated COL17A1 reframing for junctional epidermolysis bullosa.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current gene-editing approaches for treatment of recessive dystrophic epidermolysis bullosa (RDEB), an inherited, severe form of blistering skin disease, suffer from low efficiencies and safety concerns that complicate implementation in clinical settings. We present a strategy for efficient and precise repair of RDEB-associated mutations in the COL7A1 gene. We compared the efficacy of double-strand breaks (induced by CRISPR/Cas9), single nicks, or double nicks (induced by Cas9n) in mediating repair of a COL7A1 splice-site mutation in exon 3 by homologous recombination (HR). We accomplished remarkably high HR frequencies of 89% with double nicking while at the same time keeping unwanted repair outcomes, such as non-homologous end joining (NHEJ), at a minimum (11%). We also investigated the effects of subtle differences in repair template design on HR rates and found that strategic template-nicking can enhance COL7A1-editing efficiency. In RDEB patient keratinocytes, application of double-nicking led to restoration and subsequent secretion of type VII collagen at high efficiency. Comprehensive analysis of 25 putative off-target sites revealed no off-target activity for double-nicking, while usage of Cas9 resulted in 54% modified alleles at one site. Taken together, our work provides a framework for efficient, precise, and safe repair of COL7A1, which lies at the heart of a future curative therapy of RDEB.
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