The Royzen Research Group is interested in developing new synthetic and imaging tools for RNA research. The interdisciplinary work on these projects involves chemical synthesis of nucleoside analogs, characterization of their photophysical properties, solid phase synthesis of RNA strands containing unnatural nucleosides and live cell imaging. Recently, we developed a nonchromatographic procedure for synthesis and purification of long RNA oligonucleotides, containing nucleobase modifications. In collaboration with Sheng Lab (Chemistry) and Fuchs Lab (Biology) we are exploring this approach towards development of artificial mRNAs that contain m1A and m6A modifications.
We are collaborating with Shekhtman Lab to develop transition metal-based NMR probes to study RNA-protein interactions in live cells using paramagnetic NMR techniques. The probes can be covalently attached to RNA in the vicinity of the protein’s binding site. These probes are capable of attenuating NMR signal intensities from protein residues localized in proximity to the paramagnetic probe as the result of RNA-protein interactions. The extent of the attenuation is related to the probe’s proximity, thus allowing us to construct the protein’s contact surface map. This new paradigm has been applied to study binding of HIV-1 nucleocapsid protein, NCp7, to a model RNA strands.
Together with an industrial collaborator, Shasqi, Inc. we are developing a bio-orthogonal chemistry-based platform termed CAPAC (Click-Activated Protodrugs Against Cancer), capable of concentrating and activating protodrugs at a location of choice. The approach facilitates concentration of cytotoxic agents at the tumor site and, in contrast to existing targeted therapies, does not rely on endogenous cellular or environmental markers. The CAPAC platform involves a biomaterial that is strategically implanted near a tumor. The biomaterial can react with systemically administered protodrugs converting them into active cytotoxic agents leading to clear therapeutic benefits. In 2021, Shasqi started Phase I clinical trials [NCT04106492] to test the compounds developed during our collaboration.