Request for Information: Sequence Defined Polymer Synthesis with Molecular Machines for Microsystems Applications DARPA-SN-25-92

The precise synthesis of sequence-defined polymers holds the potential to revolutionize a wide variety of fields by enabling unprecedented control over physical properties at the molecular scale. In nature, the templated synthesis of perfectly sequence-defined polymers enables essential functions such as information storage in the form of DNA and chemical catalysis in the form of protein-based enzymes. Within the cell, the template-directed synthesis of biological polymers is accomplished via molecular machines such as DNA polymerase and ribosomes. These machines have evolved unique performance characteristics such as exquisite substrate recognition, very fast reaction kinetics, low error rates, and high processivity. However, these machines are limited in the breadth of chemistries they can realize. Despite decades of research, synthetic chemistry methods still lag behind the efficiency and versatility of biological systems, and struggle with throughput, polymer length, and the error rate. Conversely, the repurposing of natural molecular machines for the synthesis of chemically diverse sequence defined polymers outside of the cell has largely failed for several reasons. These include lack of robustness, limited chemical bond forming potential (i.e. peptide and phosphodiester bonds), solvent incompatibility, scalability and cost. DARPA seeks to understand potential novel methods, approaches and platforms capable of marrying the exquisite selectivity, processivity, and throughput of molecular machines with the chemical diversity, scalability, and robustness of synthetic chemistry methods to produce novel, high-value sequence defined polymers.