Madrid -Arn-Messejero is one of the terms with which the world became familiar during the Covid-19 pandemic. Then he associated with some of the vaccines that marked the turning point and today to a wide field of research, from cancer to infectious diseases.
The RNA-mensajero (mRNA) or messenger ribonucleic acid is a type of molecule that transports genetic information necessary so that in the cells the proteins that allow us to live can be manufactured.
With RNA -based therapies, cells can cause proteins that help the immune system to fight or avoid some diseases.
“The body creates the medicine itself,” the researcher Pedro Berraondo, from the top University of Navarra (northern Spain), explains to Efe.
The best known example is the vaccines of Pfizer-Bionntech or modern against the coronavirus, which contain instructions to create a protein similar to the Spike, which uses the Sars-COV-2 virus to enter the human cells, thus the immune system creates antibodies and, in case of infection, they act.
These vaccines saved millions of lives and were formulated in record time, a rush that was possible because it was investigated by the Arnm technique and some of the scientists who put their bases, such as Katalin Karikó and Drew Weissman, have received, among many other awards, the Nobel and the princess of Asturias.
Pandemia, a revulsive
Long before the pandemic, in 2016, the top University of Navarra already collaborated with modern biotechnology in a preclinical study of RNA -based therapies for intermittent acute porphyria, a rare genetic disease of liver origin, Berraondo recalls.
The pandemia “was a revulsive” for research, because many people doubted that these therapies were possible or useful, “he says,” and was demonstrated, “in a very short time, that it was an effective, safe technology and could occur to the large scale that demands the vaccination of a large part of the world’s population.”
The technique is based on creating lipid nanoparticles, which contain a synthetic MRNA sequence, which enter the cells with orders to produce a certain protein, this will trigger an answer by the host immune system, tells Efe Montserrat Plana, a researcher at the Biomedical Research Institute August Pi i Sunyer (Idibaps).
Five years after the start of pandemic, world research focuses especially on two fields. One is vaccines for infectious diseases such as flu (or combined with this and COVID-19), Zika, malaria or syncitial respiratory virus, with rehearsals in different phases.
In the case of the syncitial respiratory virus, it indicates, both the European drug agency, and the American FDA have approved for its commercialization a vaccine for people over 60 years.
Plana, an immunology specialist in the HIV field, works, within a strategy for this disease, in the development of an immunogen (a substance that could induce a specific immune response) based on RNAm, as a first step towards a therapeutic vaccine for that disease.
Personalized therapies
The other more active research field is that of therapeutic and personalized vaccines for cancer, “where there has been very important findings” in areas such as melanoma or pancreas, and there are also essays for lung or colon.
The fastest application is advancing is like adjuvant after removing a tumor to avoid recurrence. It is -Punta Berraondo- “where they are most successful and where it is expected to approval for use this year.”
These therapeutic vaccines ‘teach’ the immune system to identify and attack cancer cells, from neoantigens (specific proteins of that tumor in each patient) which allows the vaccine to be personalized, explains flat.
Berraondo coordinates the Arnmune Project for preclinical research for the development of Arnm -based cancer, designing complex molecules to activate the immune system and faced with the tumor.
“The patient’s immune system does not detect the tumor well and does not act against him, what we do is educate him to see the tumor as something dangerous that he has to eliminate,” he says.
Rare diseases are also in the spotlight, with research in various phases of cystic fibrosis therapies, Duchenne’s muscular dystrophy or propionic acidemia
A very high security profile
The two researchers underline the versatility of this technique and above all, that they have “a very high security profile” and is not integrated into the genes of those who receive them, so it does not modify genetic information, although, like any medication, it is not exempt from side effects.
Berraondo indicates that “it allows speed in the manufacture of a specific medication for each patient, since design, synthesis and production are accelerated.”
Research also faces challenges, because MNA is a very unstable molecule, hence vaccines against COVID-19 will be preserved at temperatures below zero and that these medications have to inject.
The challenge is, he points out, how from such an unstable molecule a medicine is made. This is achieved through multiple improvements such as the use of modified RNMs.
In addition, the expression of RNM will always be transitory, “it will last a few days.” In the case of a vaccine an initial dose can be administered and then those of memory, but for a genetic disease there will be repeated administrations, “which can be a disadvantage against other gene therapy strategies.”