A University of Cincinnati (UC) research team led by biomedical engineering professor Peixuan Guo, has recently released two articles in the online journal, Molecular Therapy, describing how he has developed large RNA nanoparticles. He has also tested their safety in transporting medication to targeted cells.
According to Guo, RNA therapy needs RNA to be produced in large quantities. The researchers used a bipartite approach to develop large RNA molecules. They discovered during this process that pRNA could be created from two bits of small RNA modules.
Guo is the Dane and Mary Louise Miller Endowed Chair of biomedical engineering. He is the director of the National Cancer Institute (NCI) Alliance for Nanotechnology in Cancer Platform Partnership Program at the university. The team has used various methods to develop a 117-base pRNA molecule that consisted of interfering small RNA (siRNA) that destroy genes in cells.
US's Peixuan Guo amd his team
The pRNA particles that were created to contain siRNA live for five to 10 hours in animals. They are non-toxic and do not yield immune response. The enhanced time they stay in the body enables drug creation and the laboratory tests of RNA nanoparticles prepare the foundation for it as medication.
Peixuan Guo says RNA nanoparticles should measure between 15 and 50nm, big enough to remain in the body and not enter untargeted cells, which will cause toxicity. They should however be small enough to penetrate the diseased cells with assistance from cell surface receptors.
The team reports in the second paper titled, ‘Assembly of Therapeutic pRNA-siRNA Nanoparticles Using Bipartite Approach’, that they have utilized two artificial RNA nano-particles to develop the 117-base pRNA, which then arrayed itself with other pRNA nano-particles to work in the bacteriophage phi29 viral engine to enclose DNA.
This technique was able to address the limitations of dimensions in chemical synthesis of RNA nanoparticles. The nanoparticles thus created could transport and release drugs to cells and destroy the genes in them. This feature enables further chemical alterations of RNA to target specific target cells reliably.
The second paper titled, ‘Pharmacological Characterization of Chemically Synthesized Monomeric phi29 pRNA Nanoparticles for Systemic Delivery,’ shows that it was easy to create altered three-dimensional pRNA nanoparticles using the two-piece method. The altered pRNA withstood common enzymes that targeted and weakened RNA and maintained their chemical state and metabolism.
The nanoparticles remained non-toxic when targeting diseased cells in animals without causing an immune response, thus allowing the nanoparticles to enter cancer cells in clinical tests. Guo said the research revealed that uncoated pRNA nanoparticles possessed pharmacological features essential for an efficient delivery system to the cells.