Trial reportMolecular therapy : the journal of the American Society of Gene Therapy2010
First-in-human mutation-targeted siRNA phase Ib trial of an inherited skin disorder.
Trial report in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 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
103 citing papers in PubMed, 261 citations in OpenAlex.
- Treatment Landscape for Epidermolysis Bullosa Simplex: A Review of Established and Emerging Therapies.Pediatric dermatology · 2026Review
- Allele-selective von Willebrand factor silencing.Research and practice in thrombosis and haemostasis · 2026Article
- Allele-specific RNAi therapy corrects an extracellular matrix defect in Schuurs-Hoeijmakers syndrome.American journal of human genetics · 2025Article
- Advances in locally administered nucleic acid therapeutics.Bioactive materials · 2025Review
- The future of siRNA-mediated approaches to treat von Willebrand disease.Expert review of hematology · 2025Review
- Strengthening Public Health Systems to Combat the Rising Threat of Nipah Virus: A Call for Global Preparedness and Response.Advances in experimental medicine and biology · 2025Review
- Keratins 6, 16, and 17 in Health and Disease: A Summary of Recent Findings.Current issues in molecular biology · 2024Review
- Pachyonychia Congenita: A Research Agenda Leading to New Therapeutic Approaches.The Journal of investigative dermatology · 2024Review
- En route towards a personalized medicine approach: Innovative therapeutic modalities for connective tissue disorders.Matrix biology : journal of the International Society for Matrix Biology · 2023Review
- Hydrogel-Forming Microneedles with Applications in Oral Diseases Management.Materials (Basel, Switzerland) · 2023Review
- Nanoparticles for Topical Application in the Treatment of Skin Dysfunctions-An Overview of Dermo-Cosmetic and Dermatological Products.International journal of molecular sciences · 2022Review
- Development of versatile allele-specific siRNAs able to silence all the dominant dynamin 2 mutations.Molecular therapy. Nucleic acids · 2022Article
- Clinical Applications of Short Non-Coding RNA-Based Therapies in the Era of Precision Medicine.Cancers · 2022Review
- Abnormal keratin expression pattern in prurigo nodularis epidermis.Skin health and disease · 2022Article
- Gene therapy and gene correction: targets, progress, and challenges for treating human diseases.Gene therapy · 2022Review
- Genotype‒Structurotype‒Phenotype Correlations in Patients with Pachyonychia Congenita.The Journal of investigative dermatology · 2021Article
- Investigational Treatments for Epidermolysis Bullosa.American journal of clinical dermatology · 2021Review
- Future Perspectives of Oral Delivery of Next Generation Therapies for Treatment of Skin Diseases.Pharmaceutics · 2021Review
- Formulation-based approaches for dermal delivery of vaccines and therapeutic nucleic acids: Recent advances and future perspectives.Bioengineering & translational medicine · 2021Review
- Ex vivo gene modification therapy for genetic skin diseases-recent advances in gene modification technologies and delivery.Experimental dermatology · 2021Review
43 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
The rare skin disorder pachyonychia congenita (PC) is an autosomal dominant syndrome that includes a disabling plantar keratoderma for which no satisfactory treatment is currently available. We have completed a phase Ib clinical trial for treatment of PC utilizing the first short-interfering RNA (siRNA)-based therapeutic for skin. This siRNA, called TD101, specifically and potently targets the keratin 6a (K6a) N171K mutant mRNA without affecting wild-type K6a mRNA. The safety and efficacy of TD101 was tested in a single-patient 17-week, prospective, double-blind, split-body, vehicle-controlled, dose-escalation trial. Randomly assigned solutions of TD101 or vehicle control were injected in symmetric plantar calluses on opposite feet. No adverse events occurred during the trial or in the 3-month washout period. Subjective patient assessment and physician clinical efficacy measures revealed regression of callus on the siRNA-treated, but not on the vehicle-treated foot. This trial represents the first time that siRNA has been used in a clinical setting to target a mutant gene or a genetic disorder, and the first use of siRNA in human skin. The callus regression seen on the patient's siRNA-treated foot appears sufficiently promising to warrant additional studies of siRNA in this and other dominant-negative skin diseases.
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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.