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RNA Nanotechnology in Cancer Therapy
University of Kentucky

Principal Investigators: Peixuan Guo, Ph.D., and John Rossi, Ph.D.

Project Summary

RNA molecules' diversities in function and structure make it particularly attractive as a building block for bottom-up assembly in nanotechnology and nanomedicine. Dr. Peixuan Guo's team has engineered a new nanotechnology platform, which is based on the RNA-skeleton of the bacteriophage phi29's DNA packaging nanomotor. This motor is central to translocating the bacteriophage DNA genome and is built from stable dimers and trimers of packaging RNA known as pRNA. Currently, Dr. Guo’s team is elucidating the principles underlying the RNA/RNA interactions in RNA nanoparticle assembly using phi29 motor pRNA system and RNA junction motifs to build polyvalent RNA oligomers containing combinations of aptamers, siRNA, ribozymes, ligands, imaging markers, or drugs for cancer cell recognition.

This new approach aims to screen for stable and high affinity RNA aptamers that target and enter cancer cells specifically. Additionally, RNA is notoriously unstable in biological systems making its implementation as a therapeutic platform untenable. Recent work from this Platform Partnership has created modified RNA nucleotides, fluorinated at the 2' position. pRNA made from these modified ribonucleotides was shown to be highly resistant to degradation while maintaining their biological activity. Progress of this kind keeps the door open for this innovative platform for future nanomedical applications.

Project Goal

The goal of this project is to fabricate RNA nanoparticles to incorporate therapeutic siRNA, aptamers, and ribosomes to accomplish targeted delivery for lung, ovarian, and liver cancers and leukemia.