Developing a new class of backbone modified oligonucleotides

This project aims to design, synthesize and evaluate a novel class of oligonucleotides. Oligonucleotides have emerged as a revolutionary tool in modern diagnosis and therapy of a wide range of physiological processes. Existing backbone-modified oligonucleotides suffer from poor enzymatic stability, which results in undesired side effects. The proposed research will resolve issues of selectivity and stability, as well as provide a common platform for small and large-scale synthesis of improved oligonucleotides. The technologies developed in this project will provide advanced tools to understand various mechanisms involved in genetic disorders and will have numerous applications in future diagnostics and therapeutics. The principle focus of this project is fundamental bioorganic and solid phase chemistry for oligonucleotides synthesis. The project also involves pharmacological and biophysical evaluation, which will be performed in collaboration with pharmacology team within the group, thus enabling students to acquire interdisciplinary skills and knowledge. This project aims to develop a new class of backbone-modified oligonucleotides as an efficient and common platform for the synthesis of antisense molecules. This new chemistry will result in both synthetically and biologically improved oligonucleotides as enhanced diagnostic and therapeutic agents. This work will establish a foundation for the future of improved antisense molecules for applications in numerous therapeutic areas.