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Transposon-mediated gene transfer into adult and induced pluripotent stem cells KU Leuven
Transposon technology is a particularly attractive non-viral gene delivery paradigm that allows for efficient genomic integration into a variety of different cell types. In particular, transposon-mediated gene transfer is a promising tool for stem cell research, by virtue of its ability to efficiently and stably transfer genes into adult and induced pluripotent stem (iPS) cells. Moreover, transposons open up new perspectives for ...
Regression and stabilization of advanced murine atherosclerotic lesions: a comparison of LDL lowering and HDL raising gene transfer strategies KU Leuven
Both reductions in atherogenic lipoproteins and increases in high-density lipoprotein (HDL) levels may affect atherosclerosis regression. Here, the relative potential of low-density lipoprotein (LDL) lowering and HDL raising gene transfer strategies to induce regression of complex murine atherosclerotic lesions was directly compared. Male C57BL/6 LDL receptor (LDLr)(-/-) mice were fed an atherogenic diet (1.25% cholesterol and 10% coconut oil) ...
Intratumoral gene transfer of immunomodulatory antibody combinations: a preclinical proof-of-concept study KU Leuven
Immune checkpoint inhibitors have emerged as a new promising treatment modality for cancer, as these monoclonal antibodies (mAbs) have been shown to enable durable responses in patients with various advanced and metastatic tumors. Still, a large proportion of cancer patients are refractory to this type of immunotherapy, which has led to a surging interest in combination treatments to improve response rates. These combination treatments, however, ...
State of play and clinical prospects of antibody gene transfer KU Leuven
Recombinant monoclonal antibodies (mAbs) are one of today's most successful therapeutic classes in inflammatory diseases and oncology. A wider accessibility and implementation, however, is hampered by the high product cost and prolonged need for frequent administration. The surge in more effective mAb combination therapies further adds to the costs and risk of toxicity. To address these issues, antibody gene transfer seeks to administer to ...
Gene Transfer for Inherited Metabolic Disorders of the Liver: Immunological Challenges KU Leuven
Hepatocytes are a key target for gene transfer directed at correction of inborn errors of metabolism. The theoretical potential of hepatocyte-directed gene transfer contrasts with the hurdles for clinical translation of this technology. Innate immune responses following gene transfer are initiated by recognition of pathogen-associated molecular patterns by pattern recognition receptors like Toll-like receptors. Adaptive immune responses may ...
The role of liver sinusoidal cells in hepatocyte-directed gene transfer KU Leuven
Hepatocytes are a key target for gene therapy of inborn errors of metabolism as well as of acquired diseases such as liver cancer and hepatitis. Gene transfer efficiency into hepatocytes is significantly determined by histological and functional aspects of liver sinusoidal cells. On the one hand, uptake of vectors by Kupffer cells and liver sinusoidal endothelial cells may limit hepatocyte transduction. On the other hand, the presence of ...
Beneficial effects of selective HDL raising gene transfer on survival, cardiac remodelling, and cardiac function after myocardial infarction in mice KU Leuven
Post-myocardial infarction (MI) ejection fraction is decreased in patients with low high-density lipoprotein (HDL) cholesterol levels, independent of the degree of coronary atherosclerosis. The objective of this study is to evaluate whether selective HDL-raising gene transfer exerts cardioprotective effects post MI. Gene transfer in C57BL/6 low-density lipoprotein receptor (LDLr)(-/-) mice was performed with the E1E3E4-deleted adenoviral vector ...
Lipid Lowering and HDL Raising Gene Transfer Increase Endothelial Progenitor Cells, Enhance Myocardial Vascularity, and Improve Diastolic Function KU Leuven
BACKGROUND: Hypercholesterolemia and low high density lipoprotein (HDL) cholesterol contribute to coronary heart disease but little is known about their direct effects on myocardial function. Low HDL and raised non-HDL cholesterol levels carried increased risk for heart failure development in the Framingham study, independent of any association with myocardial infarction. The objective of this study was to test the hypothesis that increased ...
Exposure of ciprofloxacin-resistant Escherichia coli broiler isolates to subinhibitory concentrations of a quaternary ammonium compound does not increase antibiotic resistance gene transfer Research Institute for Agriculture, Fisheries and Food Ghent University
Resistance to antibiotics threatens to become a worldwide health problem. An important attributing phenomenon in this context is that pathogens can acquire antibiotic resistance genes through conjugative transfer of plasmids. To prevent bacterial infections in agricultural settings, the use of veterinary hygiene products, such as disinfectants, has gained popularity and questions have been raised about their contribution to such spreading of ...