A5051594346- Neonatal Respiratory Health Research
- RNA Interference and Gene Delivery
- Cystic Fibrosis Research Advances
- Asthma and respiratory diseases
- CRISPR and Genetic Engineering
- Immune Response and Inflammation
- Respiratory viral infections research
- Immune cells in cancer
- Virus-based gene therapy research
- Energy Harvesting in Wireless Networks
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Pediatric health and respiratory diseases
- RNA and protein synthesis mechanisms
- IL-33, ST2, and ILC Pathways
- Viral gastroenteritis research and epidemiology
- Advanced biosensing and bioanalysis techniques
- Respiratory and Cough-Related Research
- Tracheal and airway disorders
- Bone fractures and treatments
- Hemoglobinopathies and Related Disorders
- RNA Research and Splicing
- Bone Tissue Engineering Materials
- Parasites and Host Interactions
- CAR-T cell therapy research
- RNA regulation and disease
University Children's Hospital Tübingen
2010-2020
University of Tübingen
2010-2020
Children's Hospital
2013
Ludwig-Maximilians-Universität München
2005-2011
Children's Clinical University Hospital
2007
University Hospital Ulm
2005
Max Planck Institute of Psychiatry
2003
The Cas9/guide RNA (Cas9/gRNA) system is commonly used for genome editing. mRNA expressing Cas9 can induce innate immune responses, reducing expression. First-generation mRNAs were modified with pseudouridine and 5-methylcytosine to reduce responses. We combined four approaches produce more active, less immunogenic second-generation mRNAs. First, we developed a novel co-transcriptional capping method yielding natural Cap 1. Second, screened nucleotides in identify modifications that increase...
Objective The generation of acinar and ductal cells from human pluripotent stem (PSCs) is a poorly studied process, although various diseases arise this compartment. Design We designed straightforward approach to direct PSCs towards pancreatic organoids resembling progeny. Results Extensive phenotyping the not only shows appropriate marker profile but also ultrastructural, global gene expression functional hallmarks pancreas in dish. Upon orthotopic transplantation into immunodeficient mice,...
Summary Neonates show an impaired anti-microbial host defence, but the underlying immune mechanisms are not understood fully. Myeloid-derived suppressor cells (MDSCs) represent innate cell subset characterized by their capacity to suppress T immunity. In this study we demonstrate that a distinct MDSC with neutrophilic/granulocytic phenotype (Gr-MDSCs) is highly increased in cord blood compared peripheral of children and adults. Functionally, isolated Gr-MDSCs suppressed proliferation...
Abstract Pseudomonas aeruginosa persists in patients with cystic fibrosis (CF) and drives CF lung disease progression. P. potently activates the innate immune system, mainly mediated through pathogen-associated molecular patterns, such as flagellin. However, host is unable to eradicate this flagellated bacterium efficiently. The underlying immunological mechanisms are incompletely understood. Myeloid-derived suppressor cells (MDSCs) generated cancer proinflammatory microenvironments capable...
Chemically modified mRNA is capable of inducing therapeutic levels protein expression while circumventing the threat genomic integration often associated with viral vectors. We utilized this novel tool to express regulatory T cell transcription factor, FOXP3, in a time- and site-specific fashion murine lung, order prevent allergic asthma vivo. show that Foxp3 rebalanced pulmonary helper responses protected from allergen-induced tissue inflammation, airway hyperresponsiveness, goblet...
Whereas cigarette smoking remains the main risk factor for emphysema, recent studies in β-epithelial Na(+) channel-transgenic (βENaC-Tg) mice demonstrated that airway surface dehydration, a key pathophysiological mechanism cystic fibrosis (CF), caused emphysema absence of smoke exposure. However, underlying mechanisms remain unknown. The aim this study was to elucidate formation triggered by dehydration. We therefore used expression profiling, genetic and pharmacological inhibition, Foerster...
Recently, a new asthma susceptibility gene, GPRA (G-protein-related receptor for asthma), has been identified by positional cloning. Initial association studies in Finnish and Canadian population suggested an with elevated serum IgE levels.In large, nested case-control study, associations between polymorphisms, asthma, levels were analyzed.Using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology, 1,872 German children aged 9 to 11 years (including 624 and/or...
Gene therapy has always been a promising therapeutic approach for Cystic Fibrosis (CF). However, numerous trials using DNA or viral vectors encoding the correct protein resulted in general low efficacy. In last years, chemically modified messenger RNA (cmRNA) proven to be highly potent, pulmonary drug. Consequently, we first explored expression, function and immunogenicity of human (h)CFTR encoded by cmRNAhCFTR vitro ex vivo, quantified expression flow cytometry, determined its YFP based...
Abstract Cystic fibrosis (CF) lung disease is characterized by infection with Pseudomonas aeruginosa and a sustained accumulation of neutrophils. In this study, we analyzed 1) the expression MyD88-dependent TLRs on circulating airway neutrophils in P. aeruginosa-infected CF patients, non-CF bronchiectasis noninfected healthy control subjects 2) studied regulation TLR functionality vitro. TLR2, TLR4, TLR5, TLR9 was increased compared patients. On neutrophils, TLR5 only that significantly...
β-Thalassemia is an inherited hematological disorder caused by mutations in the human hemoglobin beta (HBB) gene that reduce or abrogate β-globin expression. Although lentiviral-mediated expression of and autologous transplantation a promising therapeutic approach, risk insertional mutagenesis low transgene apparent. However, targeted correction HBB with programmable nucleases such as CRISPR/Cas9, TALENs, ZFNs non-viral repair templates ensures higher safety profile endogenous control. We...
Abstract β-hemoglobinopathies are caused by abnormal or absent production of hemoglobin in the blood due to mutations β-globin gene ( HBB ). Imbalanced expression adult (HbA) induces strong anemia patients suffering from disease. However, individuals with natural-occurring cluster related genes, compensate this disparity through γ-globin and subsequent fetal (HbF) production. Several preclinical clinical studies have been performed order induce HbF knocking-down genes involved repression...
The chitinase-like protein YKL-40 was found to be increased in patients with severe asthma and chronic obstructive pulmonary disease (COPD), two conditions featuring neutrophilic infiltrates. Based on these studies a previous report indicating that neutrophils secrete YKL-40, we hypothesized plays key role cystic fibrosis (CF) lung disease, prototypic disease. aim of this study (i) analyze levels human murine CF (ii) investigate whether single-nucleotide polymorphisms (SNPs) modulate...
Membranes are an integral component of guided bone regeneration protocols. This pre-clinical study was aimed at enhancing the bioactivity collagen membranes by incorporating plasmid DNA (pDNA) or chemically modified RNA (cmRNA) encoding morphogenetic protein-9 (BMP-9). In addition, we also endeavored to harness regenerative potential periosteum creating perforations in membrane. Nanoplexes polyethylenimine (PEI)-nucleic acids (PEI-pDNA PEI-cmRNA BMP-9) were incorporated into commercially...
Background: Common genetic variations in toll‐like receptor 2 (TLR2), an innate pathogen recognition receptor, may influence the development of atopic diseases. So far, very little is known about role rare TLR2 mutations these Objective: We investigated functional properties six amino acid changes (and one change a pseudogene) and studied their effect on sensitization disease. Methods: identified leading to from databases. Functional effects variants were analyzed by NF‐κB‐dependent...