Research
The Stewart Lab harnesses the structural and functional programmability of RNA for the design, synthesis, and characterization of RNA materials. RNA is a promising molecule with a wide range of applications due to its inherent biological functionality. However, there are significant challenges in developing RNA-based diagnostics and therapeutics, such as rapid degradation, intracellular delivery, and unwanted immunogenicity. We apply concepts from biology, chemistry, nanotechnology, and engineering to understand fundamental RNA self-assembly principles and build nano- and microstructures capable of interfacing with biological systems. The Stewart Lab uses computational models and experimental approaches for the design and synthesis of RNA materials that are robust, stimuli-responsive, and capable of controlling cell fate to advance applications in molecular sensing and regenerative medicine.
Current Projects
Self-assembly of chemically modified RNA
RNA materials must be stable and nuclease-resistant to be useful in biological or therapeutic setting. RNA is prone to degradation largely due to the presence of an active 2’-OH, making it more susceptible to hydrolysis of the adjacent phosphodiester bond by nucleases and metal ions. This project aims to chemically modify RNA to build nuclease resistant assemblies and to extract thermodynamic parameters to refine computational methods for improved RNA secondary structure prediction.
Stimuli-responsive RNA materials
Stimuli-responsive or “smart” materials have great potential towards biosensors, diagnostics, and therapeutic drug delivery applications. The diverse collection of RNA sequences and tertiary structures that interact with different biological targets make RNA an attractive candidate as a stimuli-responsive material. This project aims to design scalable RNA monomeric units that undergo nanoscale changes to elicit microscopic and macroscopic changes for sensors and diagnostics.
Bioactive RNA assemblies
Bioactive materials elicit specific biological responses from cells, tissues, and organisms. siRNAs and miRNAs are noncoding RNAs with significant roles in gene expression. siRNA and miRNA have been investigated as novel classes of therapeutic treatments for illness and infections. The delivery of these RNA molecules is a challenge due to poor stability, low targeting and cellular uptake. This project aims to investigate the usefulness of RNA assemblies as a platform to deliver functional RNAs to modulate biological activity.
Funding
Matter-to-Life Seed Grant, Alfred P. Sloan Foundation, 2023
