ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
Ex-vivo gene therapy restores LEKTI activity and corrects the architecture of Netherton syndrome-derived skin grafts.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 72 citations in OpenAlex.
- Dysregulated proteolytic cascades in Netherton syndrome: from molecular pathology to preclinical drug testing.The Journal of pathology · 2026Review
- Skin Barrier Dysfunction in Chronic Dermatoses: From Pathophysiology to Emerging Therapeutic Strategies.Cureus · 2025Review
- Inborn errors of immunity with atopic phenotypes in the allergy and immunology clinic: a practical review.Current opinion in allergy and clinical immunology · 2025Review
- Embryo and fetal gene editing: Technical challenges and progress toward clinical applications.Molecular therapy. Methods & clinical development · 2024Review
- Cytosine Deaminase Base Editing to RestoreJID innovations : skin science from molecules to population health · 2023Article
- Article
- Tailored treatments in inborn errors of immunity associated with atopy (IEIs-A) with skin involvement.Frontiers in pediatrics · 2023Review
- Review
- Future Perspectives of Oral Delivery of Next Generation Therapies for Treatment of Skin Diseases.Pharmaceutics · 2021Review
- Ex vivo gene modification therapy for genetic skin diseases-recent advances in gene modification technologies and delivery.Experimental dermatology · 2021Review
- Netherton Syndrome in Children: Management and Future Perspectives.Frontiers in pediatrics · 2021Review
- Challenges in Treating Genodermatoses: New Therapies at the Horizon.Frontiers in pharmacology · 2021Review
- Efficient CRISPR-Cas9-Mediated Gene Ablation in Human Keratinocytes to Recapitulate Genodermatoses: Modeling of Netherton Syndrome.Molecular therapy. Methods & clinical development · 2020Article
- Genetic activation of Nrf2 reduces cutaneous symptoms in a murine model of Netherton syndrome.Disease models & mechanisms · 2020Article
- Toward Combined Cell and Gene Therapy for Genodermatoses.Cold Spring Harbor perspectives in biology · 2020Review
- Allele-Specific Small Interfering RNA Corrects Aberrant Cellular Phenotype in Keratitis-Ichthyosis-Deafness Syndrome Keratinocytes.The Journal of investigative dermatology · 2020Article
- Article
- Lentiviral Engineered Fibroblasts Expressing Codon-Optimized COL7A1 Restore Anchoring Fibrils in RDEB.The Journal of investigative dermatology · 2016Article
- Long-term skin regeneration from a gene-targeted human epidermal stem cell clone.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Gene and cell therapy for children--new medicines, new challenges?Advanced drug delivery reviews · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Netherton syndrome (NS) is a debilitating congenital skin disorder caused by mutations in the SPINK5 gene encoding the lymphoepithelial Kazal-type-related inhibitor (LEKTI). It is characterized by defective keratinization, recurrent infections, and hypernatraemic dehydration with a mortality rate of about 10% in the first year of life. Currently, there are no curative treatments for NS. We have developed a HIV-1 based, self-inactivating lentiviral vector to express SPINK5 in keratinocytes as part of an ex-vivo gene therapy strategy for NS. High transduction efficiency was achieved in NS keratinocytes and reconstitution of LEKTI expression was confirmed in previously deficient cells. These genetically corrected keratinocytes were further tested in an in vitro organotypic culture (OTC) system and in vivo mouse/human skin engraftment model. Results showed correction of epidermal architecture in both OTCs and regenerated skin grafts. Importantly, the results from corrected skin grafts indicated that even where detectable LEKTI expression was restored to a limited numbers of cells, a wider bystander benefit occurred around these small populations. As LEKTI is a secreted protein, the genetically modified graft may provide not only an immediate local protective barrier, but also act as a source of secreted LEKTI providing a generalized benefit following ex-vivo gene therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.