Researchers at Mirus Bio Corporation have developed a technique to target specific cells with a genetic "silencing switch," known as RNA interference (RNAi), which blocks the production of disease-causing proteins inside those cells.
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.
Details of this breakthrough have just been published in the online Early Edition of the Proceedings of the National Academy of Sciences under the title "Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes". Mirus Bio, which was founded in 1995, specializes in nucleic acid chemistry and delivery systems for RNAi- and gene-based therapies.
"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, PhD, 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."
Researchers have been quick to recognize a wide range of potential medical applications for RNAi. 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.
"The industry's excitement over potential therapeutic and research applications of RNA interference continues to grow. Our siRNA polyconjugate technology represents a major breakthrough in delivery, and positions us at the heart of what has become one of the most exciting medical advances of the decade," 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," Smestad said.
In addition to Dr. Rozema, the groundbreaking work on Dynamic PolyConjugates at Mirus Bio was led by Drs. David Lewis and So Wong, Mr. Darren Wakefield and Jason Klein, along with critical contributions from Drs. Jon Wolff, James Hagstrom and colleagues.