“MRNA vaccines played a key role in mastering the Covid-19 pandemic. However, MRNA itself is an extremely unstable molecule. This does not affect the safety of therapy, but limits its effectiveness, e.g. reduces the time of action” – explains Prof. Andrzej Dziembowski from the RNA biology laboratory at the International Institute of Molecular and Cell Biology (IimCB) in Warsaw, one of the main authors of the study.
MRNA molecules contained in vaccines work in the same way as natural MRNA (information or matrix RNA) found in our cells – they are a matrix for protein production.
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“After administering the vaccine intramuscularly, MRNA from the vaccine goes to immune cells that produce protein S (protein present on the surface of the SARS -COV -2 coronavirus). Our body learns to recognize them. Thanks to this, if we later come across a real virus, the body will be ready to react and stop the development of the disease” – explained Dr. Seweryn Mroczek from Iimcb and the University of Warsaw.
Due to the instability of MRNA, the vaccine based on it is quite limited.
Prof. Dziembowski explains that A particularly important role in the stabilization of mRNA molecule and protein production, which is saved in it, plays the so -called POLI (A) tail. It is located at the end of each MRNA and consists only of adenine. That is why a team of scientists under the direction of prof. Dziembowski in cooperation with researchers from other campus units. He analyzed, How the tails of POL (A) change in mRNA, which is present in popular vaccines used during the pandemic – Comirnaty and Spikevax. For this purpose, researchers used the so -called Nanopora sequencing, which allowed direct reading of the sequence of mrna vaccine molecules, including POL (A) tails.
“We have created special software for analyzing data from sequencing therapeutic MRNA molecules, focusing on the metabolism of POLI (A) tail” – commented Dr. Paweł Krawczyk, who in the research group Prof. Dziembowski was responsible for computing methods.
Until now it was assumed that the tail could only shorten. Polish scientists have shown that the TENT5A enzyme plays a key role in lengthening the POLI (A) tail. He participates in the addition of bricks (i.e. adenine molecules) to the tail of the MRNA. It is present in some cells of our body, primarily in those that produce a lot of proteins then secreted outside the cell (so -called secretion). These are e.g. osteoblasts producing collagen necessary for bone formation.
“Extending the tail of the POLI (A) is like an hourglass reversal – it buys additional time, thanks to which MRNA works much longer in the cells” – explained Dr. Krawczyk. That is why researchers described the TENT5A polymerase as a time machine for MRNA.
“We have proved that tent5a makes MRNA molecules more stable, which allows for more long -lasting and effective production of antigens – substances triggering the body's immune reaction” – added Dr. Krawczyk.
Team prof. Dziembowski also observed which body cells play the most important role in the action of MRNA vaccines. These are macrophages, a type of immune cells that are responsible for capturing and neutralizing “intruders”.
“It is mainly in macrophages that protein is created in the mRNA vaccine, which is necessary to cause immune response and immunity,” said the specialist.
As he explained, after serving the muscle vaccine, macrophages go to the puncture site, take MRNA transferred in special lipid molecules and then produce the antigen saved in them.
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“When there is no Tent5A enzyme in macrophages, the vaccine is not so durable, less antigen is created and the immune response is weaker” – explained prof. Dziembowski.
He emphasized that the stabilization of the MRNA molecule by the TENT5A enzyme is a universal mechanism, which is why it has great potential for medicine. The Polish discovery opens the way to develop more durable vaccines and MRNA -based drugs.
“In great generalization, you can make an MRNA, which will be an ideal substrate for the TENT5A enzyme, and at the same time stop the mechanisms that cause mRNA degradation” – explained prof. Dziembowski. He noted that his team already has ideas for using his discovery in medicine.
