Delivery technology breakthrough for RNAi therapeutics

Researchers at US-based Mirus Bio Corporation have developed a technique to target RNA interference (RNAi) at specific cells.

Mirus Bio, which was founded in 1995, specialises in nucleic acid chemistry and delivery systems for RNAi- and gene-based therapies.

In a first proof-of-concept demonstration, Mirus scientists targeted liver cells and switched off their ability to produce "bad" cholesterol. This delivery platform could also be used as a foundation for RNAi therapeutics to disable cancer cells, viruses, and genes that cause other metabolic diseases, among a broad range of potential applications.

"The lack of effective systemic administration has been the primary impediment to development of RNAi therapeutics for diseases affecting internal tissues and organs," says Dr David Rozema, 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, such as in key liver cells or inside a tumor. Moreover, injected genetic material is quickly cleared from the body. Mirus researchers have overcome these problems by assembling tiny synthetic molecules, called Dynamic PolyConjugates, that shield their genetic cargo as they home in on target cells.

One stumbling block to successfully administering RNAi-based medicines has been finding a way to shield siRNA until it reaches its intracellular target. Mirus Bio researchers have found a way to shield siRNA by attaching it to a new 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 messenger RNA. The scientists also attach a masking agent that prevents the siRNA from being recognised as foreign. Finally, targeting molecules are incorporated that preferentially attach to target cells and prevent unwanted interactions with non-target cells.

"Our siRNA polyconjugate technology represents a major breakthrough in delivery,' commented Russell Smestad, Mirus Bio's president. "Not only do we have a great technology, but more than a decade of work in the nucleic acid field has enabled us to build what we believe is the strongest intellectual property portfolio in the industry covering polymer-based siRNA in vivo delivery."