Monday, May 20, 2024
5/20/2024
¿ DESCRIPTION (provided by applicant): Technology to deliver molecules "on demand" that bind to targets or catalyze reactions of a technologist's choosing would have enormous commercial value in research, manufacturing, and medicine. Thus, this has been a "holy grail" of molecular science for a half century. Even today, chemical theory is inadequate to support de novo design of receptors, ligands, or catalyst having useful affinities or catalytic power. Thus, many have sought to bring Darwinism into the laboratory. Here, the hope is to re-create, under control of a technologist, the evolutionary processes that create the powerful receptors, ligands, and catalysts found in Nature. One approach to create laboratory Darwinism was begun by Gold, Szostak, and others to exploit the intrinsic ability of natural DNA and RNA (collectively xNA) molecules to direct their own replication. These and others developed the technology that we "laboratory in vitro evolution" (LIVE), which places libraries of xNA molecules under laboratory selection pressure to extract those that bind to targets. Unfortunately, because natural xNA molecules have only four building blocks with few functional groups, they have low information density, ambiguous folding, and little intrinsic functional power, and therefore have seen little commercial use. Using synthetic biology and a second generation artificially expanded genetic information system (AEGIS), FfAME and Firebird scientists have created a fundamental breakthrough in LIVE technology. This involves adding, initially two but potentially up to eight, additional nucleotides to standard xNA. These can carry not only functionality found in natural amino acids, but functionality in addition to that seen in natural proteins, including antibodies, which provide current state-of-the-art technology for creating binding molecules. To lay the grounds for this commercialization proposal, we used AEGIS-LIVE to create AEGIS aptamers for customers who were seeking molecules that bind specifically to breast and liver cancer cells. This grant will fund the next logical step, commercializing AEGIS-LIVE via two overlapping business models: (a) A custom research collaboration model, where Firebird staff provide an AEGIS-LIVE service at a fee to generate receptors, ligands, and catalysts that are chosen by customers and clients. (b) A product generation model, where Firebird uses AEGIS-LIVE to generate receptors, ligands, and catalysts of its own choosing, as commercial products in their own right Phase 1 will perform AEGIS-LIVE that, for the first time, targets a specific defined molecule, glypican 3, a protein that is key to the lethality of many cancers. AEGIS-LIVE will be compared with a standard LIVE without AEGIS, as well as antibodies for the same protein target. AEGIS aptamers will be delivered to our customer, Dr. Chen Liu at University of Florida, to support his liver cancer research. As well as generating AEGIS aptamers having value in their own right, this work will demonstrate the flexibility of AEGIS-LIVE, develop supporting infrastructure, and launch commercialization of technology that NIH referees note is "a game changer".
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
