Simulation tools drive the new generation of therapies based on gene silencing
Researchers at Nostrum Biodiscovery, with the collaboration of other companies, have laid the groundwork for the systematic development of optimal RNA-binding inhibitors based on antisense oligonucleotide technology.
Proteins, intricate molecules with crucial roles in the body, are generated according to DNA-encoded instructions. Disrupted protein levels often underlie various diseases, either as their cause or consequence. A significant player in this process is RNA, acting as a messenger between DNA and proteins. At the forefront of innovative research targeting RNA to inhibit protein production is Nostrum Biodiscovery, specifically the Nucleic Acids Department led by the Dr. Vito Genna, PhD. Under his guidance, and thanks to the synergistic collaboration with the group of Prof. Modesto Orozco at IRB Barcelona, Nucleic Acid Department at Nostrum Biodiscovery has made significant strides in this field. Their groundbreaking approach involves the development of drugs designed to obstruct protein production, some of which are already on the market.
Dr. Vito Genna and his team, in collaboration with the Molecular Modelling and Bioinformatics lab at IRB Barcelona, have conducted extensive computational and experimental analyses. These efforts have resulted in predictive models capable of determining vital factors like the structure, stability, flexibility, and biological impact of RNA-targeting drugs. Central to their approach are RNA-binding molecules known as antisense oligonucleotides, which are DNA-based strands. These oligonucleotides utilize the Watson-Crick base-pairing model to bind to target RNA, thereby disrupting its function. Validation of their predictions has been carried out through rigorous in vitro experiments, in partnership with prominent biotech companies (see authorsip). Collaborations have also extended to esteemed academic institutions, including the Department of Inorganic and Organic Chemistry at the University of Barcelona and the Instituto de Química Física Rocasolano in Spain.
The overarching goal of their project is to establish guidelines for the development of optimal oligonucleotides capable of targeting the intermediary step in protein production. Through meticulous modifications, they have enhanced these molecules' thermostability, specificity, and sensitivity to cellular degradation mechanisms, showcasing precision engineering. Traditionally, oligonucleotide research has been labor-intensive and experimental, but Nostrum Biodiscovery is taking a pioneering step by developing machine-learning tools. These tools will streamline the work of researchers in this therapy domain, offering significant time and cost savings. In summary, Dr. Vito Genna's experience and the cutting-edge research at Nostrum Biodiscovery are shaping the future of RNA-targeting therapies. Their work holds immense promise for transforming the treatment landscape of diseases characterized by abnormal protein levels, offering hope to patients across a spectrum of conditions.