University of São Paulo: Expansion of Messenger RNA Use in Treatments Marks Advancements in Science
The use of messenger RNA in science represented one of the biggest signs of hope against Covid-19, as the technology was used in the production of some vaccines. Despite having been studied for decades, the application of this technology only had global repercussions in this pandemic scenario. Since then, new studies involving the use of messenger RNA have been and are being carried out to produce vaccines and treatments against different types of diseases.
According to João Agostinho Machado Neto, professor at the Institute of Biomedical Sciences (ICB) at the University of São Paulo, messenger RNA — or mRNA — is an extremely important molecule in the process of gene expression. “Messenger RNA works as an intermediary between DNA, which contains information, genetic instructions, and proteins, which perform a variety of functions in our body”, he comments.
The professor explains that understanding how messenger RNA works helped science explain how the flow of genetic information works and how the information contained in DNA is transmitted and translated into characteristics of an individual, whether in the context of health or disease. According to him, an important nucleic acid process during research is its transcription stage — the mechanism by which the information contained in DNA is transmitted.
Main use in science
Machado Neto explains that vaccines produced with this technology use a synthetic version of the virus’s messenger RNA, which will instruct human cells to produce the viral protein, in addition to training the immune system to recognize it, capable of triggering an immune response, similar to a real infection. In the case of vaccines against Covid-19, the expert explains that the messenger RNA is designed to encode the Spike (S) protein of the sars-cov-2 coronavirus.
“Messenger RNA has proven to be a promising and versatile tool for developing vaccines and other treatments because of its unique ability to instruct cells to produce specific proteins. This success is due, in part, to the ease and speed of producing a messenger RNA molecule for the targets of interest”, he states.
Despite its impact on the use of vaccines, the professor says that its role in science goes far beyond that, due to its versatility. Among its other possible applications is the use of this technology in gene therapies, in which messenger RNA is modified to correct genetic mutations or to encode specific therapeutic proteins and stimulate their production.
Furthermore, Machado Neto cites the importance of mRNA in gene expression studies, capable of showing how genes are expressed in different conditions and cell types, and can provide valuable information about the functioning of the human organism and the development of diseases. “Thus, message RNA is a powerful tool in science, with applications ranging from vaccine development to biomedical research”, he adds.
Other applications and research
In oncology, the professor explains that there are studies on ways to use messenger RNA to induce immune system cells to recognize and attack cancer cells. In this way, mRNA would be responsible for encoding specific proteins — such as tumor-associated antigens, proteins overexpressed in tumor cells, or neo-antigens, found only in these cells and resulting from mutations —, in addition to encoding therapeutic proteins, with the potential to inhibit tumor growth or induce the death of cancer cells.
In immunotherapy, which uses chimeric antigen receptor T cells (CAR-T), the use of messenger RNA to express the chimeric antigen is a promising approach for some types of cancer — helping to destroy even tumors that lack an antigen specific —, as Machado Neto states. “Messenger RNA has the potential to revolutionize cancer treatment, offering innovative therapeutic approaches that exploit the ability of cells to produce specific proteins or modulate gene expression in a precise and targeted manner to combat the growth and spread of tumors”, he adds.
The professor also talks about other therapeutic clinical studies, with different areas of activity, such as the production of vaccines against infectious diseases other than Covid-19 (influenza, zika, HIV, among others), the treatment of genetic diseases (covid-19 muscular dystrophy, Duchenne and sickle cell anemia) and the treatment of autoimmune diseases (rheumatoid arthritis and multiple sclerosis).
Regarding the studies, the expert cites the existence of 745 of them, 12 involving Brazilian research groups, with nine related to vaccines for covid-19, one on obesity, one on HIV infection and hepatitis-C virus, in which mRNA is used as a biomarker, and one for oncology patients. The last one deals with a clinical trial for the development and application of a vaccine using autologous dendritic cells, subjected to electroporation with mRNA from the WT1 gene. This therapy would be used as an adjuvant in the treatment of hematological malignancies and aims to delay the progression of the disease or its recurrence, in addition to increasing patient survival.
“Given that messenger RNA is a molecule easily destroyed in our body, research is looking for increasingly effective, safe and cheap tools to increase the stability of mRNA-based technologies. In the current paradigm, it is difficult to project which diseases will benefit from therapies based on messenger RNA, but the numbers are certainly encouraging and this field, in full expansion, could change the clinical course of diseases that are currently a challenge for science”, he concludes. .