Lecture 2: Spherical Nucleic Acids: Empowering the Digital Drug Design Revolution
Abstract: Over two decades ago, nucleic acid therapeutics emerged as a promising new technology for treating diseases with a known genetic basis. In recent years, nucleic acids have been identified as sequence-specific regulators of the immune system. However, issues pertaining to their stability, toxicity, and delivery have dramatically limited their application and thus slowed the growth of the field. Indeed, the vast majority of nucleic acid drugs that are currently being developed target diseases that can be addressed in the liver, the site where nucleic acids accumulate when systemically administered. We have discovered a new form of nucleic acids that can be actively internalized by most cell and tissue types, without the need for transfection agents, owing to their novel nanoscale architecture. These new forms of DNA and RNA, referred to as spherical nucleic acids (SNAs), consist of a dense shell of oligonucleotides conjugated to a nanoparticle core. The oligonucleotide shell of the SNAs imparts upon the conjugate material unique properties that differ from those of linear nucleic acids, such as rapid cellular uptake and increased resistance to nuclease degradation and are revolutionizing the way we study, track, and treat disease. SNAs are being used as potent gene regulation agents that can be topically delivered to the skin as well as cross the blood-brain-barrier to treat neurodegenerative conditions; they have also shown immense promise as new cancer vaccines. This presentation will describe how SNAs are steering the community toward a whole new way of thinking about digital drug design.