- Oligonucleotide-based therapeutics
- Development of small molecules to enhance oligonucleotide therapeutics
- Intracellular trafficking of antisense and siRNA oligonucleotides in cancer cells
Development of Small Molecules that Enhance the Delivery and the Pharmacological Effects of Oligonucleotides
A key impediment to oligonucleotide-based therapeutics is the difficulty in delivering these large, highly polar molecules to their sites of action in the cytosol or nucleus of tissue cells. While chemical modification of oligonucleotides and the utilization of various nanotechnology-based delivery approaches have been helpful, the delivery problem remains largely unresolved. We have taken an orthogonal approach to this problem and have developed small molecule compounds that enhance the functional delivery and pharmacological effectiveness of oligonucleotides by manipulating their intracellular trafficking.
Intracellular Trafficking of Antisense and siRNA Oligonucleotides in Cancer Cells
Antisense and siRNA oligonucleotides have great potential for cancer therapeutics. However our ability to use these molecules effectively is limited by lack of detailed molecular understanding of their cellular uptake and intracellular trafficking. We are addressing these issues using a variety of pharmacological, molecular and imaging techniques in single cells, multi-cellular assemblies, and tumors in vivo. This integrated approach will provide a rich stream of novel information that will enhance and expedite the development of oligonucleotides as therapeutic agents in cancer.