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Towards the application of triplex-forming oligonucleotides as therapeutic agents


   School of Pharmacy and Biomedical Sciences

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  Dr David Rusling  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Synthetic oligonucleotides are short strands of DNA that can be used to treat or manage a wide range of diseases, for example by gene silencing. 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 living cells. Although this has been hugely successful, a better strategy would be to use oligonucleotides to target genomic DNA directly to 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 duplex 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 these molecules as gene-targeting agents and this PhD project will help us in attaining that goal. 

The successful applicant will receive training in all relevant areas, including but not limited to, molecular and chemical biology. Upon starting the successful applicant will work in a newly established group led by Dr David Rusling (https://scholar.google.co.uk/citations?user=2fe0jIMAAAAJ&hl=enin) in the School of 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. Students will have access to a vast number of resources and research materials through our Graduate School.

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