ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017
Cut and Paste: Efficient Homology-Directed Repair of a Dominant Negative KRT14 Mutation via CRISPR/Cas9 Nickases.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 90 citations in OpenAlex.
- Treatment Landscape for Epidermolysis Bullosa Simplex: A Review of Established and Emerging Therapies.Pediatric dermatology · 2026Review
- Developing CRISPR-Based Therapies for Epidermolysis Bullosa: A Comprehensive Review of Current Strategies.Drugs · 2026Review
- An isogenic hiPSC-derived keratinocyte model reveals CXCL10/CXCL11 inflammatory dysregulation in epidermolysis bullosa simplex.Frontiers in cell and developmental biology · 2026Article
- Gene therapy for genodermatoses at the crossroads of innovation and clinical translation.Frontiers in bioengineering and biotechnology · 2026Review
- Clinical and genetic study of a family with epidermolysis bullosa simplex caused by a novelIntractable & rare diseases research · 2025Article
- Efficient Dual Cas9 Nickase Correction of a Prevalent PathogenicJID innovations : skin science from molecules to population health · 2025Article
- Nucleic Acid Therapy for the Skin.The Journal of investigative dermatology · 2025Review
- Gene-edited cells: novel allogeneic gene/cell therapy for epidermolysis bullosa.Journal of applied genetics · 2024Review
- Highlights of Gene and Cell Therapy for Epidermolysis Bullosa and Ichthyosis.Dermatology and therapy · 2024Review
- Pathological Mechanisms Involved in Epidermolysis Bullosa Simplex: Current Knowledge and Therapeutic Perspectives.International journal of molecular sciences · 2024Review
- Skin Development and Disease: A Molecular Perspective.Current issues in molecular biology · 2024Review
- Allele-specific CRISPR-Cas9 editing of dominant epidermolysis bullosa simplex in human epidermal stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- An anoikis-based gene signature for predicting prognosis in malignant pleural mesothelioma and revealing immune infiltration.Journal of cancer research and clinical oncology · 2023Article
- Extracellular matrix in skin diseases: The road to new therapies.Journal of advanced research · 2023Review
- A Review of CRISPR-Based Advances in Dermatological Diseases.Molecular diagnosis & therapy · 2023Review
- The Effect of Probiotic Supplementation on the Gut-Brain Axis in Psychiatric Patients.Current issues in molecular biology · 2023Review
- Keratinocytes sense and eliminate CRISPR DNA through STING/IFN-κ activation and APOBEC3G induction.The Journal of clinical investigation · 2023Article
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- Challenges of Gene Editing Therapies for Genodermatoses.International journal of molecular sciences · 2023Review
- Antisense oligonucleotides targeting exon 11 are able to partially rescue the NF2-related schwannomatosis phenotypeMolecular therapy. Nucleic acids · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
With the ability to induce rapid and efficient repair of disease-causing mutations, CRISPR/Cas9 technology is ideally suited for gene therapy approaches for recessively and dominantly inherited monogenic disorders. In this study, we have corrected a causal hotspot mutation in exon 6 of the keratin 14 gene (KRT14) that results in generalized severe epidermolysis bullosa simplex (EBS-gen sev), using a double-nicking strategy targeting intron 7, followed by homology-directed repair (HDR). Co-delivery into EBS keratinocytes of a Cas9 D10A nickase (Cas9n), a predicted single guide RNA pair specific for intron 7, and a minicircle donor vector harboring the homology donor template resulted in a recombination efficiency of >30% and correction of the mutant KRT14 allele. Phenotypic correction of EBS-gen sev keratinocytes was demonstrated by immunofluorescence analysis, revealing the absence of disease-associated K14 aggregates within the cytoplasm. We achieved a promising safety profile for the CRISPR/Cas9 double-nicking approach, with no detectable off-target activity for a set of predicted off-target genes as confirmed by next generation sequencing. In conclusion, we demonstrate a highly efficient and specific gene-editing approach for KRT14, offering a causal treatment option for EBS.
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