"The RNA is being investigated as a promising tool for the treatment of various diseases, including cancer"

mRNA (messenger ribonucleic acid) technology-based Covid-19 vaccines have demonstrated great efficacy in immunizing the population against SARS-CoV-2. We are talking about a technology that, although many may think is new and a result of scientific advances in recent years, has actually been under research for more than two decades. This foundation has precisely allowed the rapid development of serums against the coronavirus.

Originally, mRNA-based vaccine research aimed at cancer, and few could imagine that their work would contribute to addressing the greatest health crisis humanity has faced in at least the last 100 years. Now, there are increasingly voices inside and outside the scientific community that believe the progress made in recent years through the development of mRNA technology-based vaccines against Covid-19 could drive the use of this technology to accelerate clinical research related to mRNA vaccines for treating other diseases such as cancer.

Recently, the Karolinska Institute in Sweden announced the award of the 2023 Nobel Prize in Medicine to Katalin Karikó and Drew Weissman in recognition of their fundamental findings for the development of mRNA technology-based vaccines against Covid-19. We are at a crucial moment where mRNA opens the doors to new developments that can provide answers to diseases that currently lack vaccines or therapeutic options.

With the aim of understanding this technology in-depth, which has positioned biotechnology at the forefront of disruptive solutions in the field of health, we interviewed Ana Isabel Jiménez, General Director of Sylentis, a pioneer company in the development of novel drugs based on RNA interference technology.

AseBio: What is RNA?

Ana Isabel Jiménez: RNA, or ribonucleic acid, is an essential molecule in cellular biology that plays a crucial role in protein synthesis. Unlike DNA, RNA is single-stranded and exists in various forms in cells. In addition to acting as a genetic messenger to carry information from DNA to ribosomes, where protein synthesis occurs, RNA is also involved in processes such as gene regulation and the structural function of cells.

AseBio: What does messenger RNA (mRNA) technology consist of?

Ana Isabel Jiménez: The genetic information of an individual is written in their DNA, which is located in the cell nucleus and is too large to pass through the nuclear membrane. To send the information to the rest of the cell, DNA transfers the necessary information to a small molecule called messenger RNA (mRNA), which is capable of leaving the nucleus and carrying that information as a template to produce proteins. These proteins are responsible for providing structure and function to the tissues and organs of our body.

AseBio: We have seen that, in the last decades, before the arrival of Covid-19, mRNA technology was targeting cancer. Are there ongoing research efforts in this direction?

Ana Isabel Jiménez: Yes, mRNA is being investigated as a promising tool for the treatment of various diseases, including cancer. Specifically in cancer, mRNA technology offers an alternative pathway as it allows targeting key proteins involved in the development of these pathologies that could not be reached by other types of medications. In the context of cancer, RNA therapy focuses on two alternatives: firstly, with small RNA, specific genes involved in the uncontrolled growth of cancer cells can be silenced. Secondly, mRNA vaccines for cancer treatment are being developed in dozens of clinical studies, such as pancreatic cancer, colorectal cancer, and melanoma. Some vaccines are being evaluated in combination with drugs that enhance the body's immune response to tumors.

AseBio: Against what other diseases could RNA offer answers beyond cancer?

Ana Isabel Jiménez: RNA technology can be applied to all pathologies as long as we can suppress a protein that is involved in the disease. At Sylentis, we are focused on treating different eye diseases. Currently, we are researching and working with RNA interference (RNAi) technology, which allows us to silence proteins involved in eye diseases, for the treatment of dry eye disease associated with Sjögren's syndrome, age-related macular degeneration (AMD), as well as other rare retinal diseases.

AseBio: What is interference RNA (RNAi)? How does it differ from messenger RNA?

Ana Isabel Jiménez: This technology is based on gene silencing, an innovation that aims to reduce the production of abnormal or excess proteins. Small molecules of interference RNA (siRNA) block gene expression with high specificity, the process by which the information from a gene is used in the synthesis of a functional protein.

RNAi-type drugs use cellular machinery in the cytoplasm to silence messenger RNA (mRNA), which are molecular precursors of proteins. Thus, without affecting genes, they regulate their production, seeking a therapeutic benefit for diseases where the overproduction or alteration of certain proteins is a problem.

AseBio: Sylentis specializes in developing therapies using interfering RNA, a powerful tool that allows for the rational design of drugs. Can you explain how it works?

Ana Isabel Jiménez: We have our own software, SirFinderTM, which rationally designs siRNAs using mathematical algorithms and artificial intelligence (AI) algorithms based on neural networks, SVM, and machine learning to collect, refine, and reinterpret experimental data generated.

This allows Sylentis to develop specific drugs to target a disease-involved target and quickly initiate preclinical development thanks to the software that enables us to generate hundreds of specific compounds for treating a particular pathology.

AseBio: What are the research projects you are working on with RNA as the foundation?

Ana Isabel Jiménez: In addition to our focus on ophthalmic diseases, in the last two years, we have been developing siRNA for the treatment of rare diseases within the Oligofast consortium project and for pest control affecting agriculture in the AgrarIA consortium project. Moreover, since 2021, Sylentis has a pilot plant for the production of small-sized RNA (oligonucleotides), and we offer the development and manufacturing of oligonucleotides for third parties. There is a growing demand for oligonucleotides as medicines and for other uses due to their wide spectrum. Thus, we provide specific and customized services, such as developing oligonucleotides for a variety of targets.

AseBio: Following the progress experienced in recent years with RNA technology, what horizon is envisioned?

Ana Isabel Jiménez: The future of RNA technology appears extremely promising. With ongoing research and developments in this field, therapies based on RNA are expected to become an integral part of the medical arsenal against a wide range of diseases. Currently, there are 16 oligonucleotides already approved by regulatory agencies, and approximately 700 oligonucleotides are in various stages of pharmaceutical development, ranging from preclinical to clinical trials.

The ability to silence specific genes with high precision opens the door to more effective treatments, with longer-lasting effects and fewer side effects, addressing diseases that, until now, lacked therapeutic solutions.