This work, explained Dr. Guo, represents "two very important milestones in RNA nanotherapy. One problem in RNA therapy is the requirement for the generation of relatively large quantities of RNA. In this research, we focused on solving the most challenging problem of industry-scale production of large RNA molecules by a bipartite approach, finding that pRNA [packaging RNA] can be assembled from two pieces of smaller RNA modules." Dr. Guo discovered pRNA in a bacterial virus in 1987 and later demonstrated that this unique form of RNA can self-assemble into nanoparticles.
In their most recent research, Dr. Guo and colleagues detail multiple approaches for the construction of a functional pRNA molecule containing small interfering RNA (siRNA). siRNA has already been shown to be an efficient tool for silencing genes in cells, but previous attempts have produced chemically modified siRNA that last only 15-45 minutes in the body and often induce undesired immune responses.
"The pRNA particles we constructed to harbor siRNA have a half-life of between five and 10 hours in animal models, are non-toxic, and produce no immune response," said Dr. Guo. "The tenfold increase of circulation time in the body is important in drug development and paves the way towards clinical trials of RNA nanoparticles as therapeutic drugs."
Guo says the size of the constructed pRNA molecule is crucial for the effective delivery of therapeutics to diseased tissues. "RNA nanoparticles must be within the range of 15 to 50 nanometers," he said, "large enough to be retained by the body and not enter cells randomly, causing toxicity, but small enough to enter the targeted cells with the aid of cell surface receptors."
Dr. Guo also said that to his knowledge, this is the first naked RNA nanoparticles to have been comprehensively examined pharmacologically in vivo and demonstrated to be safe, as well as deliver itself to tumor tissues by a specific targeting mechanism. "It suggests that the pRNA nanoparticles without a coating have all the preferred pharmacological features to serve as an efficient nanodelivery platform for broad medical applications," he noted.