A5001546897- Skin and Cellular Biology Research
- RNA regulation and disease
- Autoimmune Bullous Skin Diseases
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- RNA Research and Splicing
- Transgenic Plants and Applications
- Plant Reproductive Biology
- Hair Growth and Disorders
- Silk-based biomaterials and applications
- Dermatological and Skeletal Disorders
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- MicroRNA in disease regulation
- Extracellular vesicles in disease
- Asthma and respiratory diseases
- Immunotherapy and Immune Responses
- Cardiac Fibrosis and Remodeling
- Nail Diseases and Treatments
- Allergic Rhinitis and Sensitization
- Circular RNAs in diseases
- Viral Infectious Diseases and Gene Expression in Insects
- Molecular Biology Techniques and Applications
- Wnt/β-catenin signaling in development and cancer
- Neurogenetic and Muscular Disorders Research
EB House Austria
2016-2025
Paracelsus Medical University
2016-2025
University of Salzburg
2003-2007
Medical University of Graz
2006
Salk Institute for Biological Studies
2005
Epidermolysis bullosa simplex (EBS) refers to a heterogeneous group of inherited skin disorders characterized by blister formation within the basal cell layer. The disease is marked variations in phenotype severity, suggesting co-inheritance genetic modifiers. We identified three deleterious variants HMCN1 that co-segregated with more severe 20 individuals EBS caused mutations KRT14, encoding keratin 14 (K14). codes for hemicentin-1. Protein modeling, molecular dynamics simulations, and...
Summary Background Several fungal species are known to cause severe respiratory and cutaneous allergic diseases . Extracts from several allergenic fungi used for in vivo vitro tests, as standard preparations still not available. Objective The aims define the pattern of IgE reactivity an population with symptoms; determine influence different extract on diagnostic results; evaluate whether there exists a relationship between specific immunoblots. Methods Skin prick tests were applied cohort...
With the ability to induce rapid and efficient repair of disease-causing mutations, CRISPR/Cas9 technology is ideally suited for gene therapy approaches recessively dominantly inherited monogenic disorders. In this study, we have corrected a causal hotspot mutation in exon 6 keratin 14 (KRT14) that results generalized severe epidermolysis bullosa simplex (EBS-gen sev), using double-nicking strategy targeting intron 7, followed by homology-directed (HDR). Co-delivery into EBS keratinocytes...
Blistering in epidermolysis bullosa simplex type Dowling-Meara (EBS-DM) is associated with an inflammatory phenotype, which can be disrupted by diacerein vitro. In this pilot study we hypothesized, that a topical formulation of 1% reduces blistering. Five patients initially applied underneath both armpits. Then, each participant received diacerein-cream for one armpit, and placebo the other (randomized withdrawal). The number blisters was reduced significantly (left: -78%; right: -66%...
BackgroundEpidermolysis bullosa simplex (EBS) is a rare genetic, blistering skin disease for which there no cure. Treatments that address the pathophysiology of EBS are needed.ObjectiveCompare impact 1% diacerein cream with placebo in reducing number blisters EBS.MethodsIn randomized, placebo-controlled, phase 2/3 trial we used topical formulation to treat defined areas 17 patients. In 2-period crossover trial, patients were randomized either or 4-week treatment and 3-month follow-up period...
Dystrophic epidermolysis bullosa (DEB) is a blistering skin disease caused by mutations in the gene COL7A1 encoding collagen VII. DEB can be inherited as recessive (RDEB) or dominant (DDEB) and associated with high wound burden. Perpetual cycles of wounding healing drive fibrosis DDEB RDEB, well formation tumor-permissive microenvironment. Prolonging wound-free episodes improving quality would therefore confer substantial benefit for individuals DEB. The collagenous domain VII encoded 82...
Abstract Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1 , leading to loss or dysfunction of type‐VII collagen (C7), a protein essential for skin stability. Clinically, patients suffer from severe blistering, chronic recurrent wounds, and scarring, which predispose early onset aggressive squamous cell carcinoma. Previous studies showed that RDEB‐keratinocytes (RDEB‐KC) express high levels matrix‐metalloproteinase 9 (MMP‐9), molecule known play crucial role...
The major challenge to a successful gene therapy of autosomal dominant genetic diseases is highly efficient and specific knock-down or repair the disease-causing allele. In epidermolysis bullosa simplex-type Dowling–Meara (EBS-DM), single amino acid exchange in exon 1 keratin 14 (K14) triggers severe skin phenotype, characterized by blistering mucous membranes after minor trauma. We chose spliceosome-mediated RNA trans-splicing specifically replace exons 1–7 K14 gene. this approach, mutated...
Abstract Background Cutaneous squamous cell carcinomas (cSCC) are the primary cause of premature deaths in patients suffering from rare skin-fragility disorder recessive dystrophic epidermolysis bullosa (RDEB), which is marked contrast to rarely metastasizing nature these general population. This remarkable difference attributed frequent development chronic wounds caused by impaired skin integrity. However, specific molecular and cellular changes malignancy, whether there common players...
Junctional epidermolysis bullosa (JEB) is a debilitating hereditary skin disorder caused by mutations in genes encoding laminin-332, type XVII collagen (C17), and integrin-α6β4, which maintain stability between the dermis epidermis. We designed patient-specific Cas9-nuclease- -nickase-based targeting strategies for reframing common homozygous deletion exon 52 of COL17A1 associated with lack full-length C17 expression. Subsequent characterization protein restoration, indel composition,...
Antisense oligonucleotides (ASOs) represent an emerging therapeutic platform for targeting genetic diseases by influencing various aspects of (pre-)mRNA biology, such as splicing, stability, and translation. In this study, we investigated the potential modulating splicing pattern in recessive dystrophic epidermolysis bullosa (RDEB) patient cells carrying a frequent genomic variant (c.425A > G) that disrupts COL7A1 gene using short 2′-O-(2-Methoxyethyl) oligoribo-nucleotides (2′-MOE ASOs)....
Generalized severe epidermolysis bullosa simplex (EBS‐gen sev) is a genetic blistering skin disease in which autosomal dominant mutations either the keratin KRT5 or KRT14 genes lead to impaired function of intermediate filament cytoskeleton basal epidermis. Here we present an ex vivo RNA trans‐splicing‐based therapeutic approach correct phenotype. To mutation within exon 1 gene, using 5′‐trans‐splicing approach, where any first seven exons could be replaced by single molecule. A...
Epidermolysis bullosa (EB), a severe genetic disorder characterized by blister formation in skin, is caused mutations genes encoding dermal-epidermal junction proteins that function to hold the skin layers together. CRISPR/Cas9-induced homology-directed repair (HDR) represents promising tool for editing causal COL17A1 treatment of junctional epidermolysis (JEB).In this study, we treated primary type XVII collagen (C17)-deficient JEB keratinocytes with either Cas9 nuclease or nickase (Cas9n)...
Trans -splicing is a powerful approach to reprogram the genome. It can be used replace 5′, 3′ or internal exons. The latter has been characterized by low efficiency, as requirements promote trans are largely uncharacterized. process induced engineered 'RNA molecules' (RTMs), which target selected pre-mRNA reprogrammed via two complementary binding domains. To facilitate development of more efficient RTMs for therapeutic applications we constructed novel fluorescence based screening system....
In the treatment of genetic disorders, repairing defective pre-mRNAs by RNA trans-splicing has become an emerging alternative to conventional gene therapy. Previous studies have made clear that design binding domains corrective molecules (RTMs) is crucial for their optimal functionality. We established a reporter-based screening method allows selection highly functional RTMs from large pool variants. The efficiency and functionality screen were validated in COL7A1 gene, which mutations are...
Regenerative medicine is strictly dependent on stem cells as a source for high diversity of somatic cells. However, the isolation such from individuals suffering severe genetic skin blistering diseases like epidermolysis bullosa (EB) often associated with further organ damage. Stem were isolated 112 urine samples 21 different healthy donors, well 33 25 donors EB. The cultivation these was optimized by testing media formulations and pre-coating culture vessels collagen. identity confirmed...
To the Editor: Spliceosome-mediated RNA trans-splicing (SMaRT) has emerged as a novel technology for repair of mutations in monogenic disorders. SMaRT can be used to replace 5′, 3′, or internal sequences an exon-wise manner. For this purpose, molecules (RTMs) are engineered, which comprise (i) wild-type coding region replaced, (ii) splicing domain that includes essential elements such branch point and polypyrimidine tract, (iii) binding (BD) hybridizing selected target bring RTM transcript...