This macromolecule, properly “trained”, can transmit instructions to diseased cells to repair or defend themselves from viruses and bacteria. It was decisive for having anti-Covid vaccines in record time, it could also change oncological therapies
Swe are spectators of one Revolution of medicine that will change the world as and probably more than the discovery of antibiotics. It took a pandemic to turn the spotlight on messenger RNA, or RNA, but later
decades of research
conducted without too much fanfare, the RNAs (since there are various types) have become the protagonists of an epochal turning point that was decisive in facing Sars-CoV-2 with
vaccines
but that will soon be the key to curing many diseases, even those against which we do not have effective weapons today.
This is explained by two recent studies from Yale University, which tell the fundamental role of mRna in cells and how they can be “driven” to become vaccines or drugs through interaction with other molecules. To understand the extent of the revolution, however, we must first take a step back and learn about RNA, or ribonucleic acid, a macromolecola which is thought to have even been there very first molecule of lifeeven before DNA, the deoxyribonucleic acid which is found in the cell nucleus and which containsgenetic information. «In the genome, in the case of man, a“ book ”with about three billion and two hundred million letters, there are genes, the information units for the functioning of our organism; the alphabet with which they are written includes four letters, G, A, C and T correspond to Guanine, Adenine, Cytosine and Thymine (four nitrogenous bases). L’Rna uses the same language as DNA but a different “dialect”, in which U (Uracile) is used instead of T », he explains Stefano Gustincich, head of the Central Rna Laboratory at the Italian Institute of Technology in Genoa. “The DNA of the genome is therefore” translated “into messenger RNA, which is so called because it carries a message: it works like a computer punch card and allows the translation of genetic information, encoded in the language of DNA, into proteins , written in a still different language in which the letters are twenty amino acids. There are 25 thousand genes, but they are not all transcribed and then translated, everywhere: about 5 thousand are translated in each cell and different genes are expressed and translated in different tissues ».
The proteins that a brain cell need are different from those that make a heart cell work and the “cell traffic fighters” who decide which genes must be translated into the proteins needed each time are mRna: this would be enough to guess their importance, which, however, is even greater if possible, because as Gustincich adds: “There are actually 35,000 other genes that were discovered after the sequencing of the human genome and are transcribed but not translated: they do not lead to the formation of proteins, therefore, but they function like Rna by assembling cell organelles, regulating the expression of genes and so on. A new world to be discovered, in which we could also find numerous potential drugs».
Research on this vast set of “non-coding” genes began a few years ago, but much earlier it was understood that mRna could be a good target for new therapies thanks to its central role in the functioning of each cell. For decades, researchers have been trying to interfere with mRNAs but, as he explains Roberto Burioniprofessor of Microbiology and Virology of the Vita-Salute San Raffaele University of Milan: «Rna is much less stable than DNAwhich is preserved for years and years (just think of the investigations of the scientific police, which can reopen cases from decades ago by recovering biological material on which to analyze the DNA, ed): l’Rna degrades immediately, so it is difficult to manipulate it in the laboratory. Furthermore, it is not “tolerated” and is immediately eliminated by our organism, which sees it as a danger signal: it is no coincidence, because many viruses have an RNA genome “. Sars-CoV-2 is an Rna virus, as well as the hepatitis A and Dengue, yellow fever and hepatitis C viruses: injecting an mRna as such hoping to use it to interfere with biological processes is therefore impossible, because it doesn’t survive long enough to have an effect. The turning point came in 2005when it was discovered that it is possible to defuse the alarm signal from the RNA by replacing the letter U of its alphabet with a slightly different “pseudo-U”: thus the immune system no longer considers an external mRna as an enemy, which can act in cells such as a vaccine, if it carries information into the body to produce proteins of a germ against which an immune response is desired, or a drug, if it produces missing or deficient proteins or if it interferes with the translation process of the genome ( see also on the following pages).
The applications are so many as to make one’s head spin because, as Gustincich adds, «All the drugs available today target no more than a thousand proteins, that is, no more than a thousand genes out of the total of 25 thousand coding; using mRna-based technologies, on the other hand, means being able to interact with any gene, even with the other 35,000 non-coding ones ». All with an approach of extreme elegance in its (apparent) simplicity: that’s enough know the sequence of the target gene, which leads to an unwanted disease-causing protein, to a protein that the immune system must recognize, or to a missing or deficient protein, to create an mRna in the test tube that in the first case “appears” to the one that makes the wrong protein produce, thus inactivating the molecule in an effective and super-precise way; in the second case it carries the information to produce the protein and make it known to the immune system; in the third, it becomes the template on which to produce the protein you need. All with a simple, rapid and easily controllable biochemical synthesis process, because there is no need to use yeasts, bacteria or other microorganisms as happens when, for example, hormones or proteins have to be produced in vitro: in fact it is little more than following a recipe, assembling ingredients that any molecular biologist has in his laboratory.
The differences in the organs
“Now we are trying to understand how to send the mRna-drugs in the different organs: we can deliver them to the liver, but the goal is to take them elsewhere too”, Gustincich points out. The studies underway to find strategies to do this or suitable “transporters” are now many and recently, for example, a group of researchers from the University of Tokyo has discovered that to get mRna into the brains of mice, many can be combined mRna in very dense balls then mixed with polyethylene glycol, a molecule without toxic effects already widely used that creates a kind of external barrier that allows the balls to travel in the blood and get to act in the brain.
April 4, 2022 (change April 4, 2022 | 11:33)
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