Over the past few years, in order to treat several diseases, research aimed at blocking protein production by RNA has intensified. Now, a study published in the journal Nucleic Acids Research has conducted computational and experimental analyses to produce predictive models that can determine the structure, stability, flexibility and biology of RNA-targeted drugs. The study has been led by Modesto Orozco, professor at the Faculty of Chemistry of the University of Barcelona and head of the Molecular Modeling and Bioinformatics Laboratory at the Institute of Research in Biochemistry of Barcelona (IRB Barcelona) —located in the Barcelona Science Park (PCB)— in collaboration with the biotechnological company Nostrum Biodiscovery.
The experimental research part was carried out in the Experimental Bioinformatics laboratory, led by expert Isabelle Brun-Heath, at IRB Barcelona. The analyses were conducted in collaboration with international biotechnological companies —Biogen and Ionis Pharmaceuticals— as well as the Department of Inorganic and Organic Chemistry of the Faculty of Chemistry of the UB, the Institute of Biomedicine of the UB (IBUB), and the Institute of Physical Chemistry Rocasolano from the Spanish National Research Council (CSIC) in Madrid.
“The project aims to establish the guidelines for developing optimal oligonucleotides to target this intermediate step in, potentially, any protein production process. We now know some of the specific modifications these molecules must undergo to improve thermostability, specificity, and sensitivity to degradation by cellular mechanisms”, notes Orozco, professor at the UB Department of Biochemistry and Biomedicine.
"The simulation tools we have developed are an example of precision engineering since we have systematically looked at every possible modification in every position of the candidate molecules in order to amplify its function. This work has only been possible thanks to the technology available at Nostrum Biodiscovery and the key collaboration of first-class partners, such as Biogen and Ionis Pharmaceuticals”, says Vito Genna, former postdoctoral researcher at IRB Barcelona and now Director of the Nucleic Acids Department at Nostrum Biodiscovery.
To date, the research on these oligonucleotides has been entirely experimental. Now, the biotech company will continue to develop these predictors to build a machine-learning tool that will guide researchers working on these types of therapies and save them time and money.