A5067090881- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Cancer Research and Treatments
- Escherichia coli research studies
- Genetic factors in colorectal cancer
- Xenotransplantation and immune response
- Pluripotent Stem Cells Research
- Cancer-related Molecular Pathways
- RNA and protein synthesis mechanisms
- Cancer Genomics and Diagnostics
- Mycobacterium research and diagnosis
- Digestive system and related health
- Adipose Tissue and Metabolism
- Colorectal Cancer Screening and Detection
- Cancer-related molecular mechanisms research
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related gene regulation
- Genetic Syndromes and Imprinting
- Gut microbiota and health
- RNA Research and Splicing
- Esophageal Cancer Research and Treatment
- Wnt/β-catenin signaling in development and cancer
- Colorectal Cancer Treatments and Studies
- Inflammatory Bowel Disease
Technical University of Munich
2015-2024
Weihenstephan-Triesdorf University of Applied Sciences
2010-2023
Rabbits are widely used in biomedical research, yet techniques for their precise genetic modification lacking. We demonstrate that zinc finger nucleases (ZFNs) introduced into fertilized oocytes can inactivate a chosen gene by mutagenesis and also mediate homologous recombination with DNA gene-targeting vector to achieve the first knockout targeted sequence replacement rabbits. Two ZFN pairs were designed target rabbit immunoglobulin M (IgM) locus within exons 1 2. mRNAs microinjected...
Abstract Xenotransplantation from pigs could alleviate the shortage of human tissues and organs for transplantation. Means have been identified to overcome hyperacute rejection acute vascular mechanisms mounted by recipient. The challenge is combine multiple genetic modifications enable normal animal breeding meet demand transplants. We used two methods colocate xenoprotective transgenes at one locus, sequential targeted transgene placement - ‘gene stacking’ cointegration engineered large...
Somatic cell nuclear transfer (SCNT) using genetically engineered donor cells is currently the most widely used strategy to generate tailored pig models for biomedical research. Although this approach facilitates a similar spectrum of genetic modifications as in rodent models, outcome terms live cloned piglets quite variable. In study, we aimed at comprehensive analysis environmental and experimental factors that are substantially influencing efficiency generating pigs. Based on considerably...
Mutation of the tumor suppressor p53 plays a major role in human carcinogenesis. Here we describe gene-targeted porcine mesenchymal stem cells (MSCs) and live pigs carrying latent TP53R167H mutant allele, orthologous to oncogenic TP53R175H mouse Trp53R172H, that can be activated by Cre recombination. MSCs allele were analyzed vitro. Homozygous deficient, on continued culture exhibited more rapid proliferation, anchorage independent growth, resistance apoptosis-inducing chemotherapeutic drug...
Significance Early detection by white-light endoscopy (WLE) is the key procedure used in clinical care to prevent colorectal cancer (CRC). In high-risk patients develop CRC, like inflammatory bowel disease, miss-rate of dysplastic lesions three times higher compared healthy individuals. this study we explored use a near-infrared probe with fluorescence as an adjunct WLE highlight adenomas. We demonstrated clinically relevant animal models carcinogenesis and ulcerative colitis that our...
Significance Genetically modified animals are crucial for functional studies and translational biomedical research. However, the generation of genome-edited large is time consuming inefficient. Here, we report transgenic pigs chickens that ubiquitously express Cas9 nuclease. The functionality was demonstrated different target genes, a variety cell types, in vivo heart developing brain. Genome editing can now easily be carried out specific organs or tissues without need to generate...
We previously produced pigs with a latent oncogenic TP53 mutation. Humans germline mutations are predisposed to wide spectrum of early-onset cancers, predominantly breast, brain, adrenal gland cancer, soft tissue sarcomas and osteosarcomas. Loss p53 function has been observed in >50% human cancers. Here we demonstrate that porcine mesenchymal stem cells (MSCs) convert transformed phenotype after activation TP53(R167H) KRAS(G12D), overexpression MYC promotes tumorigenesis. The process mimics...
Abstract The safety of most human recombinant proteins can be evaluated in transgenic mice tolerant to specific proteins. However, owing insufficient genetic diversity and fundamental differences immune mechanisms, small-animal models diseases are often unsuitable for immunogenicity testing predicting adverse outcomes patients. Most therapeutic antibodies trigger xenogeneic responses wild-type animals thus rapid clearance the drugs, which makes vivo toxicological challenging. Here we report...
We are extending the Cre/loxP site-specific recombination system to pigs, focussing on conditional and tissue-specific expression of oncogenic mutations model human cancers. Identifying location, pattern extent Cre in vivo is an important aspect this technology. Here we report pigs with a dual fluorochrome cassette under control strong CAG promoter that switches after Cre-recombination, from membrane-targeted tandem dimer Tomato green fluorescent protein. The reporter was placed at porcine...
Abstract Early and comprehensive endoscopic detection of colonic dysplasia—the most clinically significant precursor lesion to colorectal adenocarcinoma—provides an opportunity for timely, minimally invasive intervention prevent malignant transformation. Here, the development evaluation biodegradable near‐infrared fluorescent silica nanoparticles (FSN) that have potential improve adenoma during fluorescence‐assisted white‐light colonoscopic surveillance in rodent human‐scale models...
Abstract Background and Aims Crohn’s disease [CD] is a major subtype of inflammatory bowel diseases [IBD] with increasing incidence prevalence. Results studies using available small large animal models are often poorly translatable to patients, few CD show intestinal pathology. Due its similarities humans, the pig has emerged as highly suitable translational model, particularly for testing novel nutritional technological interventions. Our goal was develop physiologically relevant porcine...
<title>Abstract</title> Human pancreas development remains incompletely understood due to limited sample access constrained by ethical and practical considerations. Here we investigate whether pigs resemble humans in more closely than rodents, as such, offer a valuable alternative large-animal model. As pig organogenesis is unexplored, first annotated developmental hallmarks lineage markers of differentiation morphogenesis throughout the 114-day gestation. Building on this detailed roadmap,...
The ability to perform precise genetic engineering such as gene targeting in rabbits would benefit biomedical research by enabling, for example, the generation of genetically defined rabbit models human diseases. This has so far not been possible because lack functional embryonic stem cells and high fetal perinatal mortality associated with somatic cell nuclear transfer. We examined cultured pluripotent multipotent their support production viable animals. Rabbit putative (ES) were derived...
Abstract Recent years have seen an increasing number of genetically engineered pig models human diseases including cancer. We previously generated pigs with a modified TP53 allele that carries Cre-removable transcriptional stop signal in intron 1, and oncogenic mutation R167H (orthologous to R175H ) exon 5. Pigs the unrecombined mutant (fl develop mainly osteosarcoma but also nephroblastomas lymphomas. This observation suggested gene dysfunction is itself key initiator bone tumorigenesis,...
The PPARA (peroxisome proliferator-activated receptor-α) gene encodes a nuclear receptor that plays an important role in fatty acid catabolism by transcriptional regulation of genes involved oxidation and can be considered as candidate for fatness traits the pig. aim study was to search functional polymorphism 3' untranslated region (UTR), their association with production traits, postnatal transcript level 2 skeletal muscles (longissimus semimembranosus) 5 commercial pig breeds (Polish...
Abstract We compared gene expression in low and high-grade intraepithelial dysplastic polyps from pigs carrying an APC 1311 truncating mutation orthologous to human 1309 , analysing whole samples microdissected epithelium. Gene set enrichment analysis revealed differential of sets similar normal mucosa versus T1 stage polyps. Transcriptome many differentially-expressed genes reflecting immune infiltration. Analysis epithelium was markedly different showed increased neoplasia several known be...
Abstract Background Multiple xenoprotective transgenes are best grouped at a single locus to avoid segregation during breeding and simplify production of donor animals. Methods We used transgene stacking place human CD55 adjacent heme oxygenase 1 construct the porcine ROSA26 locus. A transgenic pig was analyzed by PCR, RT‐PCR, droplet digital immunohistochemistry, immunofluorescence, flow cytometry. Resistance complement‐mediated cell lysis caspase 3/7 activation were determined in vitro....
MicroRNAs are dysregulated in various cancers including colorectal cancer, and potential useful biomarkers of disease development. We used next generation sequencing to investigate miRNA expression profiles low- high-grade intraepithelial dysplastic polyps from pigs carrying a mutation the adenomatous polyposis coli tumour suppressor (APC1311 , orthologous human APC1309 ) that model an inherited predisposition familial polyposis. identified several miRNAs their isomiRs significantly (P <...