Development of nanomaterials for RNA delivery

Yizhou Dong, Ph.D.

Assistant Professor

College of Pharmacy

The Ohio State University

Resume:

Postdoctoral Research Fellow MIT

Ph.D., University of North Carolina at Chapel Hill

M.S. Shanghai Institute of Organic Chemistry

B.S. Peking University

Abstract:

Messenger RNA (mRNA) therapeutics have shown great promise for purpose of expressing functional proteins. However, the efficient and safe delivery of mRNA remains a key challenge for the clinical application of mRNA therapeutics. Lipid and lipid-like nanoparticles possess the potential for mRNA delivery. Based on our previous experiences, we have designed TBT derivatives, which are composed of a phenyl ring, an amide linker, and three amino lipid chains. We applied an orthogonal experimental design to investigate the impacts of formulation components on delivery efficiency. We evaluated four parameters: lipids, helper lipid, cholesterol, and PEG-lipid. Theoretically, four parameters can give 256 combinations. By utilizing the orthogonal experimental design, we are able to rank the effects of the four components with only 16 combinations and predict the best combination (Lipid 20%, DOPE 30%, and Cholesterol 40%). After two rounds of optimization, we are able to improve over 100-fold of delivery efficiency of mRNA encoding luciferase in vitro. Moreover, we studied the effects of PEG-lipid on particles size and stability. Finally, lead materials displayed efficient mRNA delivery in mice.

Time: July 12th 2016, 14:00pm

Venue: Medical Sciences Building, B321

Host: Prof. Xu Tan

举办单位：生命科学联合中心