Dynamic RNA Nanotechnology

Niles A. Pierce

Division of Biology & Biological Engineering, Division of Engineering & Applied Science

California Institute of Technology

The programmable chemistry of nucleic acid base-pairing plays central roles in the biological circuitry within living organisms and provides a rich design space for the emerging discipline of dynamic nucleic acid nanotechnology. Nucleic acid molecules can be engineered to interact via prescribed hybridization cascades to execute diverse functions including catalysis, amplification, logic, and locomotion. To date, these efforts have been primarily directed at engineering DNA devices and circuits that operate in vitro. By contrast, synthetic RNA hybridization cascades have been relatively little-explored, yet hold great promise for engineering programmable signal transduction in vivo. Because biological RNAs interface with diverse endogenous pathways, small conditional RNAs (scRNAs) that interact and change conformation to transduce between detection of programmable RNA inputs and production of biologically active, programmable RNA outputs provide a conceptually appealing framework for engineering programmable conditional regulation in living organisms. This talk will describe: 1) mechanistic design elements that can be combined in diverse ways to engineer shape and sequence transduction with scRNAs,
2) a physically sound, computationally efficient sequence design algorithm for scRNA reaction pathway engineering that supports diverse user-specified sequence constraints, including biological constraints (pre-publication software available at nupack.org), 3) conceptual opportunities and practical challenges for engineering scRNA-mediated programmable conditional regulation in living cells.