Postgraduate research opportunities Towards the next generation of COVID vaccines and cancer therapeutics. The design and development of new Lipid Nano Particle delivery systems for RNA-based therapeutics: A rationally designed chemistry and microfluidics approach.

Background

There is a growing interest in the field of RNA based therapeutics which exhibit their effect by the silencing of specific genes or overexpression of therapeutic proteins. Delivery of oligonucleotides therapeutics into the patient, however, is limited due to the instability and undesirable physicochemical properties of the parent molecules. However, this may be overcome by incorporation into a lipid based nanoparticle (LNP). Typically, these nanoparticles have diameters of between 50-100 nm and are comprised of a PEGylated lipid that helps control particles size, diasteraroylphosphatidylcholine to help form the structure of the nanoparticle and cholesterol which also contributes to the structure. Most importantly, they also contain an ionisable cationic lipid that encapsulates the negatively charged oligonucleotide and helps to increase the stability of the RNA. These delivery systems have recently proved their potential as they are basis of the Pfizer and Moderna COVID-19 vaccines, however, may also be considered for use in the treatment of cancer.

Research approach

Our approach is to combine synthetic lipid chemistry with microfluidics to design tailor made ionisable cationic lipids to be incorporated into optimum LNP delivery systems for RNA cancer therapeutics and improved COVID vaccines.

In a rational approach, a series of modified ionisable lipids will be prepared, incorporated into the LNP and loaded with the specific oligonucleotide before undergoing physicochemical property investigations to determine particle size, encapsulation loading and pKa. Following potency evaluation in specific chosen cancer assays and subsequent stability studies, a structure activity relationship profile will be generated which will be used to drive forward an iterative synthesis campaign to find the optimum LNP system for use in eg. RNA cancer therapeutics, or next generation COVID vaccines..

The chemistry component of the research will be led by Dr Geoff Coxon (first supervisor) who has over 20 years in the design and method development of lipids, with the microfluidic element being led by Prof Yvonne Perrie (second supervisor), a world leader in the design, formulation and characterisation of LNPs, and the development and use of microfluidics for scale-independent manufacture.

Further information

Bench fee =  £10,000 per year