Scientists at the University of Toronto have explored a new combination therapy idea by delivering therapeutic RNA and other powerful drugs directly to cells, making treatment easier and more suitable for treating difficult conditions such as cancer and viral infections.
By-passing the late endosome
A major problem in the field of siRNA therapy has been finding a way to get these molecules into cells and to the right location without losing their activity. In the laboratory, most drug deliverables are often absorbed by cells and sequestered in endosomes before they reach their intended targets.
A team led by U of T University Professor Molly Shoichet (ChemE, IBBME) has a solution. The researchers combined siRNA with an ionizable drug, which changes its charge depending on the pH of a solution, to improve siRNA stability and cellular uptake. This unconventional but innovative method will aid in the escape of endo-lysosome by both siRNA and drug, eventually reaching their target area to exert therapeutic effects.
Synergy: RNA and Drugs in Combination
As part of this study, the team developed a nanoparticle delivery system to co-formulate small interfering RNA (siRNA) and ionizable drugs. Although siRNA can silence gene expression in disease, it is difficult to deliver these molecules intracellular and release them from degradation.
Using the protective properties of lipids, the team was able to create a barrier around the siRNA as it traveled throughout the body and prevent this RNA from being released into target cells in combination with drugs. While the synergistic action integrated a potent delivery of siRNA to the cells, it also co-integrated an immediate delivery of active ionizable drugs which could be a game changer in the association therapy for complexed diseases that demand simultaneous targeting various pathways such as cancer and viral infections.
Conclusion
The new research, from the University of Toronto team represents a significant milestone in navigating the challenges of siRNA therapy. Their discovery of a new way to co-transport therapeutic RNA and powerful drugs straight into cells is pioneering a whole new outlook on treating complex diseases like these. It is this technique that has the promise to revolutionize the landscape of personalized medicine soon, and caters us to towards precise therapeutic solutions for individual ailment status.
