“RNA technology, in the not too distant future, will also be used to treat tumors”

Before the pandemic and the subsequent arrival of messenger RNA vaccines, very little was known about scientific research and new treatments focused on RNA technology. But what exactly is it about? What processes does it involve and, above all, what kind of perspectives is it opening on the front of the most insidious diseases? We asked all these questions to Professor Stefano Vella, infectious disease specialist, researcher and lecturer in global health at the Catholic University of Rome. “Scientific research, over the last few decades, has worked intensively on gene sequencing, allowing us to develop a greater understanding of the functions of different genes,” explains Vella.

“As we know, the process that leads to the formation of the molecules that serve the functioning of our organism starts from the DNA that is translated into RNA chains which, in turn, carry the genetic information to a cellular device (the ribosomes) that produce the proteins or enzymes necessary for our survival. These proteins are generally useful and indispensable, but it can happen, in some cases, that they can be harmful (especially if in the meantime a mutation has occurred in the DNA that encodes them). In other cases they are produced insufficiently, in other cases too many are produced. From there came the idea of ​​using RNA to modify the pathological expression of some genes ».

When did interest in this kind of technique begin?

«The first works on RNA technologies date back to the 90s but it took years of studies, research and investments to be able to produce therapies that could exploit RNA technology to treat diseases or to obtain effective vaccines. The pandemic has brought to everyone’s attention, precisely because of the media hype, a very interesting technological field for medicine. We recall that in 2006 two American researchers, Fire and Mello, they won the Nobel Prize in Medicine for their studies on interfering RNA, a branch of RNA technology capable of “turning off” the “altered” gene expressions that are at the origin of many diseases ».

How long has science been investing time and resources in this area?

«The first studies on RNA date back to the 90s when, among others, two researchers (Napoli and Jorgensen) reported a type of phenomenon, called interfering RNA (RNAi), capable of potentially turning off the expression of some genes. This research area has been further developed but it took a few decades for these therapeutic approaches to become drugs. The first globally approved RNA-based (interferent) drug was Patisiran for the treatment of a rare form of amyloidosis. Subsequently other drugs were approved and, to date, there are dozens of clinical studies that aim to increase the pathologies that can be treated with this technology. I am thinking, for example, of drugs already on the market such as those for acute hepatic porphyria “.

What are the scientific sectors on which attention is focused most?

“The two big areas of RNA-based biomedical technology are the production of drugs and vaccines. In general, almost all pathologies that have a genetic etiology can potentially be treated with RNAi, which allows it to interfere with the “defective” gene expression and, therefore, act on the primary genetic cause of the disease. To cite a few examples, some of these drugs are in development for rare diseases, that is, for those diseases for which there was no therapy. But, in perspective, we can also mention treatments for hypercholesterolemia, l’hepatitis B, l’hypertension. In perspective it will be a real revolution, because RNA drugs will represent a different way of treating diseases, acting on the root causes, “Correcting” any genetic defects before they manifest themselves in a pathology. On the other hand, RNA-based technologies, as we have verified during this pandemic, can also be applied to the development of vaccines: carrying, in the ribosomes, sequences of messenger RNA that induce the production of a foreign protein, in this case the spike protein of the coronavirus, which, in turn, induces the development of specific antibodies capable of protecting against infection. Messenger RNA technology is already being applied to the development of numerous other vaccines, improving the existing ones, but also creating new ones, for the many emerging and re-emerging infectious diseases that do not yet benefit from effective vaccines “.

It has often been heard that RNA technology can truly represent the new frontier in cancer treatment. Is that so?

‘RNA technology is capable of modulating genetic expression. Since the origin of many cancers, in practice the vast majority, is based on genetic mutations, it is clear that this technology could represent the key to “turning off” bad genes and blocking the production of molecules that participate in the growth of neoplasms. Some studies have not been positive, but, as with any clinical development, these failures yield important information: I have no doubts that RNA technology will also be used to treat tumors in the not too distant future “.

Among the main fears associated with an mRNA vaccine is the idea that it may somehow “modify” the DNA of the recipient. Is this a completely unfounded suspicion?

«Yes, it is unfounded. The little bit of messenger RNA introduced with COVID vaccines can only code for the spike. It cannot “slip” anywhere, let alone alter the genetic heritage. The situation is different with regard to another extraordinary success of the research: the possibility, already present for many genetic diseases, to insert a “right” gene into the DNA of a carrier of an altered gene: something unthinkable until recently, but already real for diseases like thalassemia and some rare neurodegenerative diseases “.