UsiRNAs Work Via the RNAi Mechanism of Action but With Minimal Off-Target Activity

BOTHELL, WA -- (Marketwire) -- 08/03/09 -- MDRNA, Inc. (NASDAQ: MRNA) announced today positive data on its proprietary UsiRNA technology, demonstrating that its UsiRNAs are highly potent against metabolic disease and cancer targets in rodent models. Further, the data establish that the knockdown of these targets is achieved via an RNAi-mediated process. Of particular importance is that the data demonstrate that strategic placement of UNA (unlocked nucleobase analogs) results in the ability to manipulate, either increasing or decreasing, strand-specific activity thus minimizing off-target activity and providing the ability to impart improved drug-like characteristics to the UsiRNAs. The data are being presented today by Michael V. Templin, Ph.D., Vice President, Discovery Research and Pharmaceutical Development of MDRNA, at the IBC Drug Discovery & Development Week, Oligonucleotide Therapeutics: From Concept to Implementation, in Boston, Massachusetts.

"UNA-modified siRNAs are novel and proprietary constructs that have high potency in target mRNA reduction. In addition, we have recently determined that strategic placement of UNA in the siRNA reduces micro-RNA-like off-target activity. This observation is distinct from, and in addition to, our previous work in which we have demonstrated that UNA residues have a dramatic effect on reduction of cytokine induction by siRNA," stated Barry Polisky, Ph.D., Chief Scientific Officer of MDRNA. "We are encouraged by these significant results that demonstrate the versatility of UNA and UsiRNAs for improving the safety and specificity of RNAi, and reinforce our confidence in our UsiRNA platform."

"Repeated positive results from multiple in vivo studies in rodents using our UsiRNAs and DiLA2 delivery platform has led us to the initiation of preclinical safety and efficacy studies in non-human primates," stated J. Michael French, President and Chief Executive Officer. "We are one of a handful of companies to have initiated non-human primate studies with a liposomal-based delivery system and we look forward to reporting positive data this quarter."

About Unlocked Nucleobase Analogs and UsiRNAs

Unlocked Nucleobase Analogs (UNA) are substitutes for nucleotides that make up conventional siRNAs. UNAs have an open structure in the place of the ribose portion, making them more flexible than common nucleotides. UsiRNAs are a duplex siRNAs containing at least one UNA. UsiRNAs are fully recognized by the cellular RNAi machinery, as demonstrated by their potent activity. MDRNA has also shown that inclusion of UNA increases stability to nucleases, substantially reduces cytokine induction, and reduces passenger and guide strand-mediated off-target effects.