Analytical platform could advance mRNA medicine QC

Tokyo researchers have developed a new analytical platform based on liquid chromatography, mass spectrometry and software analysis that quantifies the structure of messenger RNA (mRNA)-based medicines. The method is an important innovation for quality control (QC) in production lines.

The platform can elucidate mRNA sequences while quantifying ‘capping’ at one end of the molecule and the integrity of the tail on the other, all vital in mRNA pharmaceuticals.  

mRNA medicines

mRNA is responsible for transmitting the sequence information stored in our DNA to ribosomes, the protein-making machinery of our cells, according to the research. Artificially designed mRNA molecules can be used as a drug which enables our cells to produce specific protein structures. This is like antigens which can trigger an immune response and act as a vaccine.

These medicines are considered much safer over competing technologies, they do not integrate onto the host cell genome and they are relatively easy to manufacture and scale up. Methods are now needed to perform quality control of this new technology in a more effective, efficient way.

The researchers stated mRNA medicines have three key components:

• The sequence, which determines what proteins are synthesised
• 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, the research stated. Currently no method that can quantify the state of all three in one go.

The team’s platform combines two important innovations. Firstly, using liquid chromatography and mass spectrometry, they carry out 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.

Then, automated analysis 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.

An innovative solution for quality control

The method is applicable to a wide range of mRNA lengths and sequences from completely different origins, allowing all three parts to be analysed 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.

The research from Tokyo Metropolitan University was published in the journal Analytical Chemistry.