Oligonucleotides as biochemical and therapeutic tools.

The laboratory of the promoter has a long-standing experience for both antisense and small interfering RNA (siRNA) research. Hallmark of this research is the substitution of 6-membered ring structures (pyranoses or hexitols) for the natural furanose sugars. While in vitro promising results have been obtained with siRNA mediated gene expression inhibition studies, some problems of selectivity and toxicity and of selective uptake and bioavailability are remaining to successfully bring the technique into the clinic. Several parts can be discerned in this program all aiming for further improvements either on the constructs themselves or in their application with the ultimate goal of further contributing to their therapeutic development. In first place, monomers with improved binding efficiency and pairing selectivity will be looked for, which hence will show reduced toxicity. Secondly, we will aim for in vivo siRNA mediated control of gene expression using a mouse model for pancreatic cancer. Finally, another goal of the project is to develop synthetis ribonucleases, where sequence-selective cleavage of target RNA strands is aimed for with the aid of synthetic constructs.

Keywords:Synthetic oligonucleotides, Ribonuclease mimics, Pancreas cancer, Hexitol nucleic acids, siRNA

Disciplines:Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences