Periodic Reporting for period 1 - SWIRL (Short, weakly interacting RNA ligands for the development of high-concentration monoclonal antibody therapeutics)
Reporting period: 2018-06-01 to 2019-11-30
The aim of this project was to prove the potential of rationally designed oligonucleotides to address the issues of solubility and aggregation in protein formulations. As the principal system of choice we chose monoclonal antibodies, some of the most important modern therapeutic agents used to combat a wide range of diseases including different neurodegenerative diseases, autoimmune disorders and cancer. For practical reasons, these proteins need to be stored and administered at extremely high concentrations. However, as is common for many proteins, such conditions frequently lead to diminished solubility, aggregation and loss of activity. Importantly, aggregation of monoclonal antibodies injected into blood stream can cause severe immunogenic effect in patients. In this project, we have experimentally studied the ability of arguably the most important interacting partners of proteins in real biological systems, the nucleic-acid molecules, to directly solubilize target proteins in a specific way. The central idea is that nucleic acids would be designed in a sequence-specific way and added to monoclonal antibodies as excipients to improve their solubility during production, storage and administration. Importantly, our approach seeks to improve the solubility of monoclonal antibodies in a powerful, novel manner, fully inspired by nature. As major results of the project, we have developed an in silico platform for designing optimal nucleic-acid binders to proteins of choice, tested our predictions in a number of relevant examples and identified optimal conditions for application. These results provide a foundation for future commercial exploitation of our idea. Importantly, in the course of the project, we have drafted and submitted a patent application covering the invention, currently in the priority year stage, with the effective date of filing on October 23 2019. Furthermore, we are currently undertaking steps in the direction of commercializing our solubilization technology. In line with this, we have established direct contacts with both local and global funding sources and are actively pursuing different options including establishing a startup or commercializing our platform via licensing of designed solubilizing oligonucleotide libraries. Given the importance of monoclonal antibodies in modern medicine, as well as the possibility of a direct extension to other proteins, our project has a potential for major societal and economic impact.