2023-10-03 05:20:00
There is a fragile and unstable molecule that is essential for human existence: it is RNA, responsible for collecting the instructions of life stored in DNA and converting them into the proteins that allow us to breathe, eat, run or read. It is an ephemeral molecule because it disintegrates quickly, but it is useful for almost everything. Even to cure patients: Covid vaccines based on messenger RNA technology – it is the body’s own cells that produce molecules with therapeutic capacity – have saved thousands of lives and their creators, researchers Katalin Karikó and Drew Weissman, have just to win the Nobel Prize in Medicine for the development of this technique. Its potential, in fact, goes beyond covid and the scientific community is already exploring its possibilities in other diseases, such as cancer, flu, HIV or autoimmune ailments.
Messenger RNA technology consists of designing a type of RNA on demand in the laboratory – with instructions for making a protein or a piece of virus, for example – so that, when introduced into the cell, this synthetic molecule is read by the cellular machinery and begins to produce the desired protein. In the case of Covid, the operation of these messenger RNA vaccines consisted of transporting the external RNA instructions into the cell so that the cells made the spike protein of the virus and it was located by the immune system.
More information
It has not been an easy path to convert the technique into an effective therapy – Karikó said that his first research was rejected until he even lost his position at the university – but the success of mass vaccination against covid with this platform has given a boost to technique. “The impressive flexibility and speed with which messenger RNA vaccines can be developed pave the way for using the new platform also for vaccines against other infectious diseases. In the future, the technology may also be used to deliver therapeutic proteins and treat some types of cancer,” the Nobel jury celebrated yesterday.
The scientific community is already working on it. A little less than a year ago, research in mice demonstrated the potential of a universal flu vaccine designed with messenger RNA technology: trials in rodents and ferrets proved that the therapy protected against all known subtypes of the influenza virus , about twenty. The authors concluded that, as with the covid vaccine, this preparation did not protect against infection, but it did protect against the most serious phase of the disease.
Karikó also pointed out, in an interview with this newspaper, that Moderna – one of the pharmaceutical companies that designed a vaccine against covid – is also developing a vaccine against the respiratory syncytial virus, which causes most bronchiolitis in the youngest children every year. winter. “This company also has two ongoing trials of a vaccine against HIV and also against the Epstein-Barr virus, which could be the cause of multiple sclerosis. There is also a new experimental vaccine against nipah [un virus emergente en Asia que tiene una mortalidad de entre el 40% y el 75%]. It is interesting that both Moderna and BioNTech [otra de las compañías que desarrolló una vacuna contra la covid] have announced that they are developing RNA vaccines against shingles. There is already one, but it costs about 800 euros. The advantage of messenger RNA vaccines is that they are cheap and can be developed very quickly,” he said.
Regarding the use of messenger RNA technology in HIV, Weissman himself was, in an interview with EL PAÍS, optimistic about the potential of this technique in an infection without a cure and with dozens of frustrated attempts in search of a vaccine. : “We have worked on HIV vaccines for many years and now we have some clinical trials with RNA vaccines and we believe that in the next six or seven years we will have an effective vaccine for HIV.”
No specific target in HIV
Julià Blanco, researcher at IrsiCaixa, agrees that “RNA technology has a place in the development of vaccines against HIV,” but is cautious: “The limiting step is to identify which antigen we have to put in the vaccine. The RNA for the vaccine will produce an HIV protein in our body that has to generate neutralizing antibodies and that is very difficult with HIV. We don’t know what protein we want. And it is very difficult for RNA to save us if we are not clear about the design of the antigen.” The scientist also emphasizes that, in the case of HIV, the implementation of a vaccine of these characteristics is complex: “HIV is a huge problem in Africa and if we have to have an impact anywhere, it is in Sub-Saharan Africa. And at that point, RNA technology, which is susceptible to temperatures [como se trata de una molécula muy inestable, las vacunas hay que mantenerlas a temperaturas muy bajas (las de la covid, a -80 grados)]perhaps it is not the best because it requires infrastructure and logistics that are difficult to transfer to Africa.”
Blanco adds, however, that what messenger RNA technology can help with is “generating vaccines very quickly.” It was seen in the pandemic: while a conventional vaccine can take about 10 years to develop, it took Moderna 42 days to have a vaccine candidate messenger RNA after China published the complete genetic sequence of SARS-CoV-2. “This technology has demonstrated its value: the speed of generating new vaccines. Building RNA is easier than a protein, which is what we did before. In RNA vaccines, you build the RNA and inject it, and the proteins are made by our own cells,” he explains.
Beyond viruses, there is also research with messenger RNA to develop vaccines against malaria, borreliosis, which is transmitted by a tick bite, and against tick-borne encephalitis.
Another field where messenger RNA technology aims to occupy a prominent place in history is in cancer. In fact, it was already being studied there before the pandemic exploded. The doctor and immunologist Ugur Sahin, founder of BioNTech – the company that developed, together with Pfizer, another of the vaccines against covid – was already testing this technology on humans to treat cancer with the intention of developing a specific vaccine for each patient. The idea was to read the tumor’s DNA, identify surface proteins (the antigens) and write a messenger RNA with the instructions to make those proteins, so that, upon entering the cell, the cellular machinery itself would create those tumor antigens. and the body’s defenses were activated against cancer.
Shy green shoots in cancer
And there are shy green shoots in this environment. At the end of last year, the pharmaceutical companies Moderna and Merck announced favorable results in their preliminary trials (phase 2b) of a messenger RNA therapy against melanoma: the companies assured that this vaccine, in combination with the immunotherapy pembrolizumab, reduces the risk by 44% of death and relapse.
These are “promising” results, says Laura Angelats, an oncologist at the Hospital Clínic of Barcelona. But she adds: “We must be cautious because it is a limited number of patients and a specific type of tumor. “We need more data and with more types of tumors.” Research is also being done in lung cancer and hepatocellular carcinoma, says Angelats, but in very early stages. “We are talking about complementary treatments to surgery, not in metastatic phases.”
In pancreatic cancer, the most lethal tumor, a messenger RNA vaccine in combination with conventional drugs caused eight patients to respond positively: the therapy managed to activate the immune system of half of the patients included in the study and, in the During the 18 months of the trial, none of the eight had a relapse. Karikó, however, was cautious: “This is progress because it was thought that it was impossible in this tumor. But the treatment only worked in half of the patients.” The researcher warned that it was a trial with few patients and could not be generalized: “The vaccine was basically their last chance. Her immune system was already very weak, although it continued to function. What we needed was to generate immunity mediated by killer T lymphocytes [una clase de glóbulo blanco]. Eight responded, and 18 months later they did not see his cancer return. Another eight did not respond and suffered a relapse. One of the patients who responded had metastases and, even so, his tumors disappeared. We do not know why. We did observe that the patients who did not respond had slightly larger tumors. Now we have to continue accumulating information and understand why some people react and others do not. “That’s science.”
Angelats insists on taking “the data with caution” and warns that this type of technology, in addition to being expensive, cannot be developed in any center, but in institutions with a high technical level. “The procedure to have a vaccine is to do a biopsy of the patient’s tumor and a blood test. These antigens that are in the tumor and not in the blood are sequenced and looked at. When they are detected, a certain number is selected and, from there, the vaccine is designed. It is personalized, for each tumor and each patient,” she explains.
The limits of this technology remain to be seen. “RNA is going to be used in more and more therapies,” Weissman predicted a little over a year ago, after receiving the Frontiers of Knowledge Award from the BBVA Foundation. “With RNA, we have been able to modify two types of immune cells inside mice and make CAR-T [una técnica que consiste en extraer las células inmunes del propio organismo, reprogramarlas y volverlas a inyectar para que reconozcan las células malignas] to cure them of cardiac fibrosis. And we are taking it to humans. “We believe we will be able to cure sickle cell anemia with a single injection of RNA.” The scientist assured that this technology is also being investigated to treat autoimmune ailments, such as lupus or rheumatoid arthritis.
You can follow EL PAÍS Salud y Bienestar in Facebook, X e Instagram.
#future #messenger #RNA #technology #scientific #revolution #won #Nobel #Health #Wellness