Good news for quality control of mRNA medications

The wide development of mRNA-based therapies requires new methods to perform quality control in a more effective, efficient way. mRNA medicines have three key components: the sequence, which determines what proteins are synthesized; the 5’-capping, which ensures that the mRNA is read efficiently during protein translation; the poly(A) tail, which dampens the immune response against the foreign mRNA itself. All three need to be in good working order for the treatment to be effective. However, there is currently no method that can quantify the state of all three in one go.

A team led by Drs Masato Taoka of Tokyo Metropolitan University and Hiroshi Nakayama of RIKEN CSRS have developed an analytical platform combining liquid chromatography, mass spectrometry and automated software analysis to quantitatively monitor the properties of mRNA molecules. The team’s platform combines two important innovations. Firstly, using liquid chromatography and mass spectrometry, they undertake a systematic comparison of different fragments of a mRNA molecule to be tested with a similarly fragmented reference mRNA labelled with a stable carbon isotope. Secondly, automated analysis using Ariadne software helps ascertain structures with the help of a sequence database. The team found that their analysis platform could successfully assign the primary structure of the reference, then rapidly identify even the most minute changes in the mRNA molecule being tested, all while yielding quantitative information on the capping and tail group.

The method is applicable to a wide range of mRNA lengths and sequences from completely different origins, allowing all three parts to be analyzed in one go. It promises unparalleled efficiency in checking for the quality of mRNA medicines, both those in action now and yet to be developed.