Optimising Product Quality of In Vitro Transcribed mRNA Therapeutics

A fully funded BBSRC/MedImmune PhD studentship is available in the Department of Chemical and Biological Engineering at the University of Sheffield, starting in October 2019.

Gene therapy offers therapeutic promise for treating many currently incurable conditions, including cancers, neurological disorders and cardiovascular diseases. However, these therapies lack the enabling technologies that support development of other biopharmaceuticals, resulting in slow speed-to-clinic and/or poor product performance. For example, the production of mRNA for mRNA-based gene therapies is currently hampered by low yields and poor product qualities. These mRNA molecules are produced by in vitro transcription (IVT) systems that comprise four biological input components: the DNA template, an RNA polymerase, ribonucleoside triphosphates and a cap analogue/capping enzyme. The functionality of, and interplay between, these biological parts determines the rate of formation of both the ‘correct’ mRNA product, and undesirable product-related impurities, such as uncapped mRNA, long/short dsRNA, and long/short ssRNA molecules. These impurities significantly impact product quality, both by hampering mRNA performance (e.g. protein produced in vivo per mRNA dose) and activating potent, undesired immune responses. The unpredictable and uncontrollable formation of these molecules is therefore a critical obstacle to successfully translating IVT mRNA therapeutics into the clinic.

This project will create new biological parts for production of IVT mRNAs, that are specifically designed to eliminate formation of product-related impurities, while also maximizing both system yield and batch-to-batch reproducibility. This is an excellent opportunity for a postgraduate student to work on a synthetic biology project with direct bioindustrial application. It is particularly suited to students with degrees in biology, bioengineering, biotechnology, or related disciplines. The student will be based in Sheffield but will have opportunities to gain experience of world-leading biopharmaceutical R&D at MedImmune in Cambridge.

There are multiple funded studentships available in my group, if you wish to be considered for more than one opportunity please state this in your application.