RxGen and Santaris Pharma Use LNA Technology to Suppress a MicroRNA in Liver of a Non-Human Primate and Safely Lower Serum Cholesterol

Hamden, CT and Hørsholm, Denmark — Business Wire March 27, 2008 — In a study published in the journal Nature today, Santaris Pharma and RxGen, Inc., a specialty pharma services company demonstrated that locked nucleic acids (LNAs) could be safely and effectively delivered to liver of African green monkeys to suppress expression of a regulatory microRNA. The study shows that an LNA that specifically binds to miR122 can readily enter the liver and suppress the target molecule. Remarkably, administration of just three doses over the course of one week markedly altered serum lipid profiles for 5-7 weeks, resulting in a 30% reduction in total cholesterol and Apolipoprotein A1, with no evidence of adverse toxicity.

“LNAs are an effective approach to gene suppression in primates,” said RxGen President & CSO Matthew Lawrence. “We are all very excited to see how experimentally straightforward and safe it was to achieve a sustained and pronounced physiologic change with knockdown of a liver gene using Santaris’ LNA technology.”

This is the first demonstration that microRNAs can be targeted in a primate and suggests that they might represent a new class of therapeutic targets in humans. Moreover, the demonstration that chemically unmodified LNAs are stable and active in non-human primates opens many possibilities for targeting genes to explore biological pathways and therapeutic targets. “This study is very exiting for us both in terms of demonstrating the power and utility of LNAs for human therapy and microRNAs as targets,” commented Sakari Kauppinen, the lead scientist on the project at Santaris Pharma.