cfaed Seminar Series

ABSTRACT:

Messenger RNA (mRNA) delivery allows to produce therapeutic protein sustainably in diseased tissue, garnering much attention for various medical applications such as mRNA vaccine, genome editing and protein replacement therapy. mRNA has two major problems: rapid degradation by nucleases and strong immunogenicity. To tackle these issues, many researchers including I vigorously develop mRNA carriers, especially by focusing on the design of cationic polymers or lipids that bind to mRNA. On the other hand, less focus is on mRNA designing. A major issue of this approach is that even subtle chemical modification of mRNA can impair protein translation activity from mRNA. My group developed novel mRNA modification method, based on hybridization of mRNA with short RNA oligonucleotides installed with proper functional moieties. This strategy allows mRNA functionalization without impairing translational activity. Using this strategy, my group succeeded in improving mRNA nuclease stability by combinational use of polycation-based carrier, and also by bundling several mRNA strands to prepare mRNA nano-assembly. Furthermore, hybridization of longer RNA to mRNA poly A region provided mRNA with immunostimulatory property without decreasing translational activity, leading to successful application to mRNA vaccine. Our strategy provides a platform for improving mRNA functionality for future therapeutic application.