RNA Nanotechnology for Drug Delivery and Formulation

16:30 - 17:05

The field of RNA nanotechnology has advanced rapidly during the past decade. A variety of programmable RNA nanoparticles with defined shape, size, and stoichiometry have been developed for diverse applications. RNA nanotechnology is the construction of nano-architectures by bottom-up self-assembly with a scaffold, ligands, therapeutics, and regulators, comprised mainly or exclusively of RNA. RNA nanoparticles can self-assemble into a homogeneous structure with defined stoichiometry. These nanoparticles with 2’- modifications are thermodynamically and chemically stable, non-toxic, and highly soluble; display favorable biodistribution and PK/PD profiles; and retain authentic folding and independent functionalities of all incorporated modules (ie. RNA aptamer, siRNA, miRNA or ribozyme). Although I proved the concept of RNA nanotechnology by bottom-up self-assembly of engineered RNA fragments in 1998 (Cell 1998; Molecular Cell 1998), it was not until recently that three major challenges became resolved concerning RNase degradation, in vivo dissociation, and immune responses. The rising popularity of RNA nanotechnology is mainly due to the following achievements: (1) introducing chemical modifications into nucleotides without significantly altering the RNA folding or self-assembly; (2) confirming the concept that RNA structures have very high thermodynamic stability and is suitable for in vivo circulation and other applications; (3) developing methods to control shape, size, and stoichiometry of RNA nanoparticles; (4) proving that the immunogenicity of RNA nanoparticles is size, shape, structure and sequence dependent and is tunable to produce either a minimal immune response that can serve as safe therapeutic vectors, or a strong immune response for cancer immunotherapy or vaccine adjuvants;  (5) decreasing cost of RNA production by chemical synthesis; (6) demonstrating the production of safe and specific targeting therapeutic RNA nanoparticles for cancer and other diseases with little or no accumulation in vital organs.

Further reading:

1) ACS Nano. 2018; in press. 2) Journal of Control Release. 2018; 276:17. 3) Nature Nanotechnology. 2018; 12:82. 4) Advanced Materials. 2016; 28:7501. 5) Molecular Therapy. 2016; 24:1267. 6) ACS Nano. 2015; 9:9731. 7) Advanced Materials. 2016; 28:100. 8) Nature Nanotechnology. 2011; 6:658. 9) Nature Nanotech. 2010; 5:833. 10) Mol. Cell. 1998. 2:149 (first paper to prove of concept of RNA Nanotechnology, featured in Cell). 11) Science. 1987; 236:690. 12) Nano Today. 2015; 10:631.

Peixuan Guo, Sylvan G. Frank Endowed Chair in Pharmaceutics and Drug Delivery Systems, The Ohio State University