Harnessing flow biocatalysis as an enabling technology for manufacturing oligonucleotide therapeutics

Oligonucleotide therapeutics are an emergent drug modality and consist of modified or unmodified short nucleic acid sequences; these include antisense oligonucleotides (ASOs), small interfering RNA (siRNAs), microRNA (miRNAs), aptamers, and DNAzymes. Notable also in recent times is the use of oligonucleotide sequences (mRNA) for the development of a vaccine for SARS CoV-2. Currently, 13 oligonucleotide therapeutics have been granted new drug approval by the U.S. Food and Drug Administration, for several different indications, and there are proposed to be over 100 further candidates under development. Whilst the field of gene-based therapies is clearly in ascendance, there are still a number of challenges that remain unsolved, for example, in the area of oligonucleotide delivery, and a requirement to explore and improve the chemistries that are used to manufacture oligonucleotides and their precursors (nucleosides/tides) – where this PhD project will focus.    

The project will combine aspects of modern synthetic carbohydrate chemistry, enzymatic synthesis, and flow technologies, harnessing the expertise of the academic team, to ensure a high standard of training and outcome. The research will be undertaken at Keele University, but involves a collaboration with the University of Manchester. You will receive training in modern organic synthesis, carbohydrate chemistry, molecular and microbiology, and flow chemistry, all geared towards the design and development of routes to deliver the required molecular targets. Transferable skills such as reporting of results orally and in writing, time management, project planning and management will also be developed. Finally, alongside this multidisciplinary training an industrial placement at Astra Zeneca is integrated into the 4-year training period.

Funding: The project is funded by Keele University and Astra Zeneca for four years - stipend and fees for UK students. Non-UK students would be required to pay the additional overseas fees themselves.

Qualifications: Applicants should have or expect a 2(i) honours degree (or an equivalent degree) in Chemistry. Any experience in synthetic organic chemistry/biocatalysis is a plus. 

Contact for further information: For informal inquiries regarding the project please contact the academic leads, Prof. Gavin Miller (g.j.miller@keele.ac.uk) or Dr Sebastian Cosgrove (s.cosgrove@keele.ac.uk) and include a CV.

Details of current research projects underway in the Miller group can be found here: https://www.millerresearchgroup.co.uk and in the Cosgrove group here: (https://www.keele.ac.uk/scps/ourpeople/chemistry/sebastiancosgrove/#research-and-scholarship). A formal application (through the advertisement) must be submitted to be considered, where applicants should provide details of their qualifications, including a CV and a personal statement.

Submission: Closing date for applications 01/02/23: Applications (and interviews thereafter) will be considered on a rolling basis and the position will be considered filled once a suitable candidate has been identified.