Overcoming challenges with large RNA and mRNA therapeutics

yi-zhang · ‎06-16-2022

How mass spectrometry enables direct characterization and sequence mapping through an automated, high-throughput workflow

As demonstrated by the development of the COVID-19 vaccine, large RNA (including mRNA) has emerged as a new class of therapeutics. However, developing analytical methods for the analysis of mRNA therapeutics has its share of challenges, including:

Risk of impurities: The enzymatic manufacturing process can generate incomplete mRNA products and other potential impurities (e.g., dsRNA).
Risk of degradation: During manufacturing and storage, mRNA can be degraded by exposure to heat, hydrolysis, oxidation, light and ribonucleases.
Limited availability: Current analytical methods to characterize mRNA are limited.
Ongoing difficulty: Method development for the analysis of large RNA and mRNA (>1000 nucleotides) is challenging.

The demand is real. Mass spectrometry can help

There’s currently significant demand for the development of new and improved analytical methods for the characterization of mRNA therapeutics.

Fortunately, mass spectrometry can help today’s labs develop an automated, high-throughput workflow for the rapid characterization and direct sequence mapping of large RNA and mRNA molecules. In a recent publication on Analytical Chemistry, Prof. Mark Dickman at the University of Sheffield described a complete workflow that achieves routine comprehensive sequence coverage from a single analysis while overcoming challenges associated with digestion, oligonucleotide separation and identification.

This workflow enables you to