Discussion

Nucleic acids not only serve as a repository of genetic information, but can also form specific ligands, enzymes and nanostructures and are potentially a rich source of powerful drugs. However, nucleic acid drugs suffer from a number of systemic shortcomings inherent in nucleic acid chemistry. These include poor biostability and low bioavailability. We have developed strategies that enable the replication and rapid evolution of nucleic acid polymers composed entirely of unnatural building blocks that confer desirable physicochemical and pharmacological properties. These synthetic genetic polymers promise to deliver tailor-made “designer” ligands and catalysts of high serum stability, defined compact structure and expanded functionality with obvious potential as a novel class of bio-therapeutics. Specifically, I'll present recent work on the discovery of novel aptamer ligands directed against a viral RNA and a protein target and composed entirely from an unnatural nucleic acid architecture that is completely resistant to degradation by serum nucleases and withstands prolonged exposure to acid without loss of structure or activity. I'll discuss the prospects of this technology to provide a new class of biotherapeutics based on an expanding range of evolvable synthetic genetic polymers.