Using nanopore sequencing to ensure the quality of mRNA vaccines

Abstract

Billions of mRNA vaccine doses have been manufactured during the COVID-19 pandemic. The removal of contaminating RNAs and inclusion of modified nucleotides reduces the innate immune response and improves the translation and performance of mRNA vaccines. Here we show how nanopore sequencing can analyse the manufacture and quality of mRNA vaccines. Nanopore sequencing enables quantitative analysis of mRNA vaccine sequences, length, and purity, including detection of off-target RNA impurities. Direct RNA sequencing can also measure the incorporation of modified nucleotides and 5’ capping of mRNA vaccines. Together, this shows how nanopore sequencing can inform best manufacturing practices, routinely monitor batch quality, and provide a detailed characterisation of the final mRNA vaccine product.