ArticlePloS one2011
Development of allele-specific therapeutic siRNA in Meesmann epithelial corneal dystrophy.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 47 citations in OpenAlex.
- Meesmann Corneal Dystrophy with Epithelial Basement Membrane Abnormalities: Clinical and Genetic Analysis of Two Families with Novel and Known Mutations inInternational journal of molecular sciences · 2026Article
- A Novel Pathogenic Variant in theJournal of clinical medicine · 2025Article
- Chemical evolution of an autonomous DNAzyme with allele-specific gene silencing activity.Nature communications · 2023Article
- A biologically stable DNAzyme that efficiently silences gene expression in cells.Nature chemistry · 2021Article
- Development of a Corneal Bioluminescence Mouse for Real-Time In Vivo Evaluation of Gene Therapies.Translational vision science & technology · 2020Article
- Corneal dystrophies.Nature reviews. Disease primers · 2020Review
- Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects.Signal transduction and targeted therapy · 2020Review
- Effective In Vivo Topical Delivery of siRNA and Gene Silencing in Intact Corneal Epithelium Using a Modified Cell-Penetrating Peptide.Molecular therapy. Nucleic acids · 2019Article
- In vivo histology and p.L132V mutation in KRT12 gene in Japanese patients with Meesmann corneal dystrophy.Japanese journal of ophthalmology · 2019Article
- Towards personalised allele-specific CRISPR gene editing to treat autosomal dominant disorders.Scientific reports · 2017Article
- Allele-specific silencing of EEC p63 mutant R304W restores p63 transcriptional activity.Cell death & disease · 2016Article
- Keratin 12 missense mutation induces the unfolded protein response and apoptosis in Meesmann epithelial corneal dystrophy.Human molecular genetics · 2016Article
- CRISPR/Cas9 DNA cleavage at SNP-derived PAM enables both in vitro and in vivo KRT12 mutation-specific targeting.Gene therapy · 2016Article
- Identification of presumed pathogenic KRT3 and KRT12 gene mutations associated with Meesmann corneal dystrophy.Molecular vision · 2015Article
- Severe Meesmann's epithelial corneal dystrophy phenotype due to a missense mutation in the helix-initiation motif of keratin 12.Eye (London, England) · 2013Article
- Allele-specific siRNA silencing for the common keratin 12 founder mutation in Meesmann epithelial corneal dystrophy.Investigative ophthalmology & visual science · 2013Article
- Allele dependent silencing of collagen type I using small interfering RNAs targeting 3'UTR Indels - a novel therapeutic approach in osteogenesis imperfecta.International journal of medical sciences · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundMeesmann epithelial corneal dystrophy (MECD) is an inherited eye disorder caused by dominant-negative mutations in either keratins K3 or K12, leading to mechanical fragility of the anterior corneal epithelium, the outermost covering of the eye. Typically, patients suffer from lifelong irritation of the eye and/or photophobia but rarely lose visual acuity; however, some individuals are severely affected, with corneal scarring requiring transplant surgery. At present no treatment exists which addresses the underlying pathology of corneal dystrophy. The aim of this study was to design and assess the efficacy and potency of an allele-specific siRNA approach as a future treatment for MECD. METHODS AND
findingsWe studied a family with a consistently severe phenotype where all affected persons were shown to carry heterozygous missense mutation Leu132Pro in the KRT12 gene. Using a cell-culture assay of keratin filament formation, mutation Leu132Pro was shown to be significantly more disruptive than the most common mutation, Arg135Thr, which is associated with typical, mild MECD. A siRNA sequence walk identified a number of potent inhibitors for the mutant allele, which had no appreciable effect on wild-type K12. The most specific and potent inhibitors were shown to completely block mutant K12 protein expression with negligible effect on wild-type K12 or other closely related keratins. Cells transfected with wild-type K12-EGFP construct show a predominantly normal keratin filament formation with only 5% aggregate formation, while transfection with mutant K12-EGFP construct resulted in a significantly higher percentage of keratin aggregates (41.75%; p<0.001 with 95% confidence limits). The lead siRNA inhibitor significantly rescued the ability to form keratin filaments (74.75% of the cells contained normal keratin filaments; p<0.001 with 95% confidence limits).
conclusionsThis study demonstrates that it is feasible to design highly potent siRNA against mutant alleles with single-nucleotide specificity for future treatment of MECD.
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.