Researchers at Mirus Bio developed a technique to target specific cells with siRNA that blocks the production of disease-causing proteins inside those cells. In a first proof-of-concept demonstration, the scientists targeted liver cells and switched off their ability to produce LDL cholesterol.
"The lack of effective systemic administration has been the primary impediment to development of RNAi therapeutics for diseases affecting internal tissues and organs," says David Rozema, Ph.D., one of the lead authors of the study. "This new delivery platform gives us a powerful tool to reach and silence the expression of any gene we might be interested in."
Although RNAi has already been used experimentally to treat a few diseases, there has been no efficient way to target specific cells where particular diseases occur, and moreover, injected genetic material is quickly cleared from the body, the company says. Mirus researchers overcome these problems by assembling tiny synthetic molecules, called Dynamic PolyConjugates™, that shield siRNA as they hone in on target cells, they report.
The Dynamic PolyConjugates include a type of polymer that not only protects the siRNA in the bloodstream but also enables it to break out of a cell's endosome, so it can interact with the mRNA and target molecules that prevent unwanted interactions with nontarget cells, Mirus explains.
The research is published in the online early edition of the Proceedings of the National Academy of Sciences.