Chromatographic separations for mRNA therapeutics: developing platform process for a new therapeutic modality

Lead Research Organisation: University College London
Department Name: Biochemical Engineering


The recent prominence of mRNA products as leading COVID-19 vaccine candidates places huge challenges on their manufacture. Success would drive the use of mRNA into a whole range of new therapeutic applications and the need for well understood manufacturing processes.
In vitro transcription (IVT) of DNA with phage RNA polymerases is currently the most efficient method to produce long sequence-specific RNA. IVT is a relatively simple procedure when compared to cell based synthesis that allows for template-directed synthesis of RNA molecules of any sequence from short oligonucleotides to those of several kilobases. The increasing importance of IVT mRNA for synthesising the encoded therapeutic protein in vivo demands the manufacturing of pure mRNA products. While the reaction can yield large quantities of RNA, it contains impurities due to various unwanted activities of the polymerases. These product-related impurities include uncapped mRNA, double-stranded RNA, and short single stranded RNA. They significantly impact product quality, both by hampering mRNA efficacy and of most concern activating immune responses.
This project seeks to address this purification challenge by first understanding the nature of product related impurities in IVT reactions and secondly on the basis of this understanding developing cost effective and scalable chromatographic separations that can remove these impurities to a specification suitable for clinical applications.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/T517793/1 01/10/2020 30/09/2025
2424139 Studentship EP/T517793/1 28/09/2020 27/09/2024 Julian Grinsted