SBIR Phase I: A computational framework to mitigate protein aggregation

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project addresses the significant and persistent challenge of protein aggregation in the development of protein therapeutics, which can impede therapeutic efficacy and increase manufacturing costs. Protein-based therapies hold immense promise for treating a wide range of diseases due to their specificity and potency. However, their development is frequently hampered by aberrant aggregation, which can lead to loss of function and immunogenic responses. This project proposes a novel computational platform that predicts aggregation-prone sites and, critically, suggest specific mutational mitigation strategies to stabilize proteins without altering their therapeutic function. The successful development of this technology has the potential to significantly reduce the time and possible cost associated with drug development, enhancing the availability of effective treatments and supporting the health and welfare of the population. This Small Business Innovation Research (SBIR) Phase I project will focus on advancing a computational platform that leverages state-of-the-art simulations and a modern understanding of the physics of protein hydration to identify and mitigate problematic aggregation sites in therapeutic proteins. The project aims to validate and enhance the platform's predictive capabilities through a comprehensive analysis involving a diverse dataset of proteins. In particular, this project will focus on developing the abilities of the technology to identify transient protein interfaces likely to mediate aggregation and to suggest rigorous mutational strategies to mitigate aggregation without disrupting biological function and therapeutic efficacy. The expected outcomes include a scientifically validated tool that can reliably predict and correct aggregation issues early in the drug development process. By improving the stability and efficacy of biologic therapeutics, this technology has the potential to have a significant commercial impact on the fast-growing biopharmaceutical market. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.