ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
Somatic correction of junctional epidermolysis bullosa by a highly recombinogenic AAV variant.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Molecular plasticity of LAMA3 across the disease spectrum: pathogenic mechanisms and clinical translation.Histochemistry and cell biology · 2026Pooled it
- Case Report: Two neonatal cases of genetically confirmed junctional epidermolysis bullosa in a tertiary care center.Frontiers in pediatrics · 2026Article
- Tailoring capsid-directed evolution technology for improved AAV-mediated CAR-T generation.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Gene-edited cells: novel allogeneic gene/cell therapy for epidermolysis bullosa.Journal of applied genetics · 2024Review
- A scalable and cGMP-compatible autologous organotypic cell therapy for Dystrophic Epidermolysis Bullosa.Nature communications · 2024Article
- Intracameral Injection of AAV-DJ.COMP-ANG1 Reduces the IOP of Mice by Reshaping the Trabecular Outflow Pathway.Investigative ophthalmology & visual science · 2022Article
- Strategies to improve safety profile of AAV vectors.Frontiers in molecular medicine · 2022Review
- Investigational Treatments for Epidermolysis Bullosa.American journal of clinical dermatology · 2021Review
- Synthetic Biology: Emerging Concepts to Design and Advance Adeno-Associated Viral Vectors for Gene Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Evaluating the Genomic Parameters Governing rAAV-Mediated Homologous Recombination.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Leading edge: emerging drug, cell, and gene therapies for junctional epidermolysis bullosa.Expert opinion on biological therapy · 2020Review
- Site-Directed Mutagenesis Improves the Transduction Efficiency of Capsid Library-Derived Recombinant AAV Vectors.Molecular therapy. Methods & clinical development · 2020Article
- Oligodendrocyte Death in Pelizaeus-Merzbacher Disease Is Rescued by Iron Chelation.Cell stem cell · 2019Article
- Epidermolysis bullosa: Advances in research and treatment.Experimental dermatology · 2019Review
- Article
- CRISPR/Cas9-Mediated In Situ Correction of LAMB3 Gene in Keratinocytes Derived from a Junctional Epidermolysis Bullosa Patient.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Regenerating human epithelia with cultured stem cells: feeder cells, organoids and beyond.EMBO molecular medicine · 2018Review
- Future of rAAV Gene Therapy: Platform for RNAi, Gene Editing, and Beyond.Human gene therapy · 2017Article
- Research Techniques Made Simple: The Application of CRISPR-Cas9 and Genome Editing in Investigative Dermatology.The Journal of investigative dermatology · 2016Review
- Allele-specific silencing of EEC p63 mutant R304W restores p63 transcriptional activity.Cell death & disease · 2016Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Definitive correction of disease causing mutations in somatic cells by homologous recombination (HR) is an attractive therapeutic approach for the treatment of genetic diseases. However, HR-based somatic gene therapy is limited by the low efficiency of gene targeting in mammalian cells and replicative senescence of primary cells ex vivo, forcing investigators to explore alternative strategies such as retro- and lentiviral gene transfer, or genome editing in induced pluripotent stem cells. Here, we report correction of mutations at the LAMA3 locus in primary keratinocytes derived from a patient affected by recessive inherited Herlitz junctional epidermolysis bullosa (H-JEB) disorder using recombinant adenoassociated virus (rAAV)-mediated HR. We identified a highly recombinogenic AAV serotype, AAV-DJ, that mediates efficient gene targeting in keratinocytes at clinically relevant frequencies with a low rate of random integration. Targeted H-JEB patient cells were selected based on restoration of adhesion phenotype, which eliminated the need for foreign sequences in repaired cells, enhancing the clinical use and safety profile of our approach. Corrected pools of primary cells assembled functional laminin-332 heterotrimer and fully reversed the blistering phenotype both in vitro and in skin grafts. The efficient targeting of the LAMA3 locus by AAV-DJ using phenotypic selection, together with the observed low frequency of off-target events, makes AAV-DJ based somatic cell targeting a promising strategy for ex vivo therapy for this severe and often lethal epithelial disorder.
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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.