Innovations in mRNA vaccine precision manufacturing

Abstract

The mRNA manufacturing industry has grown quickly to address the massive, worldwide demand for COVID-19 mRNA vaccines, as well as emerging mRNA vaccines and therapies. However, more than half of the cost and time taken to manufacture an mRNA vaccine is dedicated to onerous quality control testing. We describe how direct RNA sequencing can be used in quality control testing of mRNA vaccines and therapies. Here, different mRNA vaccines were sequenced using the Direct RNA Sequencing Kit, and basecalled using a custom Dorado model that recognises N1-methylpseudouridine, a modified nucleoside commonly used in mRNA vaccines. Our results were analysed using a custom EPI2ME pipeline, which permitted the confirmation of mRNA vaccine sequence identity, integrity (including the poly(A) tail), and purity. We show that direct RNA sequencing is ideally suited to routine quality-control testing during mRNA vaccine manufacture, for batch failure investigation, and for continuous process improvement. Fully bespoke manufacturing capability has been built from the ground up, integrating state-of-the-art electronics with silicon fab technology, combining the chemistry and biology. The company has been commercially distributing sequencing platforms since 2015, including the handheld and portable MinION and Flongle, and the high-throughput benchtop devices, GridION and PromethION. These platforms are used in more than 100 countries to understand the biology of humans and diseases such as cancer, plants, animals, bacteria, viruses, and whole environments.

Biography

Helen Gunter is a Senior Postdoctoral Fellow at the Australian Institute for Bioengineering and Nanotechnology at The University of Queensland. Collaborating with Oxford Nanopore and the BASE mRNA facility, her research aims to develop tools that improve the quality and efficacy of mRNA vaccines. Helen has diverse research and industry experience in genomics, with 17 years in genomics research in Australia and Germany, and as the Project Manager for the second largest genomics facility in the UK.