2025/10/21

CIC bioGUNE contributes to a study that uncovers key genetic information for the development of mRNA-based therapies

An international study, published in Nature Communications, has revealed a ‘hidden code’ that explains how genetic mutations alter RNA maturation. This advance opens the door to the development of RNA-based therapeutics for the treatment of rare and population-specific diseases.

Mauro D’Amato, Ikerbasque Research Professor and leader of the Gastrointestinal Genetics Research Group at CIC bioGUNE and LUM University, has contributed to the international study, led by Monash University (Australia), which uncovered genetic rules determining how mutations affect mRNA and cause disease.

The work, published in the scientific journal Nature Communications, represents a major step forward in the development of personalized mRNA-based therapies, capable of addressing under-researched diseases or those with specific incidence in certain populations.

mRNA is the molecule that acts as an intermediary between DNA and proteins, which are responsible for most cellular functions. For mRNA to fulfill its role correctly, it must undergo a process known as splicing, which removes unnecessary fragments of genetic code; when this mechanism is disrupted by mutations, the result can be the onset of severe diseases such as cancer, neuromuscular disorders, immunodeficiencies, or other clinically significant conditions.

To carry out this work, the team used SpliSER, an innovative tool developed in 2021 that can measure RNA splicing with great precision. By analyzing millions of splice sites in plants and in more than 25 species, including humans, they identified universal patterns that reveal how mutations alter this essential process.

The research team highlights that this discovery is not just a source of hope but a clear roadmap towards personalized therapies that can correct splicing defects caused by mutations, enabling the design of specific solutions for rare diseases or those linked to populations under-represented in genomic studies. This breakthrough consolidates the role of mRNA as a therapeutic tool beyond its use in vaccines and is expected to have an immediate impact on the development of new personalized medicine strategies.

“By uncovering the genetic rules of RNA maturation, this work also provides a foundation for better understanding and eventually treating common complex diseases with unmet medical needs,” notes Mauro D’Amato, Professor of Medical Genetics at LUM University and Ikerbasque Research Professor at CIC bioGUNE, member of BRTA.

The study is the result of a collaboration between the Monash Biomedicine Discovery Institute, Monash e-Research Centre, LUM University (Italy), Chinese Academy of Sciences (China), University of Melbourne (Australia), and CIC bioGUNE (Spain), and reflects CIC bioGUNE’s role as an international reference center in precision biomedicine, committed to researching complex molecular mechanisms and developing innovative solutions to improve human health.

Photograph by: © Figure created by AI using Adobe Firefly.

Reference: Craig I. Dent, Stefan Prodic, Aiswarya Balakrishnan, Aaryan Chhabra, James D.G. Georges, Sourav Mukherjee, Jordyn Coutts, Michael Gitonobel, Rucha D. Sarwade, Joseph Rosenbluh, Mauro D’Amato, Partha P. Das, Ya-Long Guo, Alexandre Fournier-Level, Richard Burke, Sridevi Sureshkumar, David Powell & Sureshkumar Balasubramanian. A basic framework to explain splice-site choice in eukaryotes. Nat. Commun. DOI: 10.1038/s41467-025-63622-9.

About CIC bioGUNE
The Centre for Cooperative Research in Biosciences (CIC bioGUNE), member of the Basque Research & Technology Alliance (BRTA), located in the Bizkaia Technology Park, is a biomedical research organisation conducting cutting-edge research at the interface between structural, molecular and cell biology, with a particular focus on generating knowledge on the molecular bases of disease, for use in the development of new diagnostic methods and advanced therapies.

About Ikerbasque
Ikerbasque - Basque Foundation for Science - is the result of an initiative of the Department of Education of the Basque Government that aims to reinforce the commitment to scientific research by attracting, recovering and consolidating excellent researchers from all over the world. Currently, it is a consolidated organization that has 290 researchers/s, who develop their work in all fields of knowledge.

About BRTA
BRTA is an alliance of 4 collaborative research centres (CIC bioGUNE, CIC nanoGUNE, CIC biomaGUNE y CIC energiGUNE) and 13 technology centres (Azterlan, Azti, Ceit, Cidetec, Gaiker, Ideko, Ikerlan, Leartiker, Lortek, Neiker, Tecnalia, Tekniker y Vicomtech) with the main objective of developing advanced technological solutions for the Basque corporate fabric.

With the support of the Basque Government, the SPRI Group and the Provincial Councils of the three territories, the alliance seeks to promote collaboration between the research centres, strengthen the conditions to generate and transfer knowledge to companies, contributing to their competitiveness and outspreading the Basque scientific-technological capacity abroad.

BRTA has a workforce of 3,500 professionals, executes 22% of the Basque Country's R&D investment, registers an annual turnover of more than 300 million euros and generates 100 European and international patents per year.

Spanish version