Next Generation Oligonucleotide Drugs for Gene Therapy

Synthetic oligonucleotides are short strands of DNA that can be used to treat or manage a wide range of diseases, for example by silencing malfunctioning genes. In recent years, various oligonucleotides have made it through clinical trials and have now reached the clinic to some fanfare. They often elicit their affects via antisense or RNAi mechanisms by acting on messenger RNA molecules and modulating protein levels inside the cell. Although this has been hugely successful, a better strategy, at least in principle, would be to use oligonucleotides to target genomic DNA directly and prevent messenger RNA expression altogether. Oligonucleotides that might prove useful in this manner are known as triplex-forming oligonucleotides, on account of their binding to specific gene sequences and generating a triplex structure. Our research group has recently overcome a long-standing problem associated with these molecules using oligonucleotides containing modified DNA bases (https://academic.oup.com/nar/article/49/13/7256/6316833?login=true). We are now at the stage of developing them as gene-targeting agents for use inside living cells and have received funding from the Academy of Medical Sciences for post-doctoral research in this area (https://www.port.ac.uk/news-events-and-blogs/news/portsmouth-researcher-awarded-share-of-ps66m-funding-to-help-develop-new-drug). 

Please get in contact with Dr David Rusling (david.rusling@port.ac.uk) if you are interested in self-funding a PhD that will feed into this research program. Our laboratory is located in the School of Medicine, Pharmacy and Biomedical Science at the University of Portsmouth. Portsmouth is a modern, multi-disciplinary University located in a dynamic and vibrant waterfront city on the south-coast of England. A successful applicant will receive training in all relevant areas, including but not limited to, molecular and chemical biology. They will have access to a vast number of resources and research materials through our Graduate School.