SBIR Phase I: Consolidated platform to engineer and produce novel biopolymers for improved biologics

Pearl Bio, Inc., Cambridge MA

Investigators

Abstract

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is the development of a next generation biomanufacturing platform that could redefine the nature of protein building blocks and become a major driver of US innovation and economic growth. By engineering new microbial organisms and their associated cellular machinery, this technology may enable the incorporation of diverse, non-native components into proteins, creating a new class of biological materials for applications in therapeutic development, biomaterial development, and other areas of biomedical research. These newly designed proteins can be specifically engineered to add desired functionalities, leading to intelligent design of novel products in the biomedical field. This Phase I project seeks to address the limitations of current approaches in this field, creating a consolidated platform able to incorporate synthetic starting materials, and characterizing how these modifications impact microbial cell growth and fitness. These advances may establish a new paradigm for design and production of next-generation products with enhanced efficacy and functionalities, driving the development of new therapeutics and materials for transformative societal, medical, and economic benefit. The proposed project will address major feasibility challenges in the development of a consolidated platform for synthesis of synthetic biopolymers containing multiple, distinct synthetic chemistries endowing novel chemical and biophysical functionality. Efforts to expand the genetic code have shown that the natural translation system is capable of selectively incorporating a wide range of synthetic amino acids (sAAs). However, several roadblocks have substantially limited the field to only one or a few instances of site-specific incorporation of sAAs. These include: biological restrictions to altering ribosome sequence, poor efficiencies of orthogonal translation systems for sAA incorporation, and unavailable open codons that have constrained biopolymer synthesis to tag-and-modify approaches or simple protein decorations. This project seeks to address these challenges in bringing this innovation to market by combining a genomically recoded organism containing engineered translation machinery with Ribo-T to enable the production of synthetic biopolymers with synthetic monomers. Additionally, this project aims to establish the technical capabilities of encoding two distinct sAAs into a single polymer. Together, these Phase I goals will advance a biomaterials platform to produce synthetic biopolymers with multiple synthetic chemistries to de-risk a path toward novel polymer biologics. 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.