Pearl Bio - Templated Biomaterials for Half-Life Extension and Therapeutic Functionalization

N. Ma
Yale University,
United States

Keywords: synthetic amino acids, genome recoding, ribosome engineering, cell-free synthesis, half-life extension, click chemistry, site-specific attachment, antibody-drug conjugates

Summary:

Pearl Bio is pioneering the design and production of the next generation of biomaterials. Harnessing a suite of proprietary synthetic biology technologies, we can biomanufacture genetically encoded materials (GEMs) to meet a range of applications in medicine, electronics, environmental sustainability, fabrics, aerospace, and beyond. Conventional chemistry can generate materials possessing unlimited functional diversity, but cannot be implemented in a template-directed manner. In contrast, biology enables template-directed materials production, yet is constrained to the 20 natural amino acids. Pearl Bio unites the precision of biology with the unlimited diversity of chemistry in a transformative platform that produces materials with tunable and evolvable properties unattainable through any other approach. Pearl Bio’s first application is in half-life extension for biologic therapeutics. We can manufacture proof-of-concept material on our platform and observe in vivo increases in half-life of up to 25-fold compared to unmodified protein. Additionally, preliminary immunogenicity studies have indicated that the unnatural amino acid used in the modification process is not immunogenic. Current Platform Progress: * Establishing broad proprietary platform for programmable GEMs production * Advancing proof-of-concept products for technology validation * Extended protein half-life in an animal model using a GEM that enables site-specific modification with fatty acids * Created tunable, self-assembling GEM-nanoparticles for applications in drug delivery and vaccines * Preliminary in vivo data demonstrates lack of immunogenicity to synthetic amino acids used in GEMs * Seeking strategic partners for development and initial investment to launch Publications: * Lajoie et al. Genomically recoded organisms expand biological functions Science. 2013;342(6156): 357. Describes genomic recoding that enables higher-efficiency in vivo unnatural amino acid incorporation. * Amiram et al. Evolution of translation machinery in recoded bacteria enables multi-site incorporation of nonstandard amino acids. Nat. Biotechnol. 2015;33: 272. Demonstrates highly efficient incorporation of unnatural amino acids at multiple sites within a protein. * Orelle et al. Protein synthesis by ribosomes with tethered subunits. Nature. 2015;524(7563):119. Describes ribosome with linked subunits, enabling engineering of ribosomes that utilize non-amino acid monomers. * Martin et al. Cell-free protein synthesis from genomically recoded organisms. Nat. Comm. 2018; 9(1):1203. Demonstrates high-yield cell-free synthesis of proteins with unnatural amino acids at multiple sites.