MDRNA Reports UNA-Modified siRNAs Effectively Silence Gene Targets in Animal Models

BOTHELL, WA--(Marketwire - December 3, 2008) - MDRNA, Inc. (NASDAQ: MRNA) announced today positive in vivo efficacy data on its proprietary Unlocked Nucleic Acid (UNA) siRNAs in animal models, demonstrating up to 90% knockdown of ApoB. In addition, the Company continues to report effective and safe delivery of its Lead Candidate for hypercholesterolemia in animal models, with no increase in blood markers of liver or kidney toxicity in single and repeat dosing studies up to 9 mg/kg. The data were presented by Michael V. Templin, Ph.D., Vice President, Discovery Research and Pharmaceutical Development of MDRNA, at the Informa Life Sciences 9th Annual Conference, EuroTIDES, in Düsseldorf, Germany.

"Our UNA technology provides a novel means of maintaining potency while increasing the specificity and safety of siRNAs," stated Dr. Templin. "UNA-containing siRNAs were highly active in the mouse ApoB model for both message inhibition and serum cholesterol reduction. Further, in in vitro studies siRNAs containing UNA moieties at strategic positions within the siRNA are highly active across diverse gene targets involved in viral infection, metabolic disease and cancer. In these cases, UNAs were fully compatible with RNAi machinery yet they decreased the potential for cytokine induction. We are extremely encouraged by these significant results and believe we have yet another unique siRNA construct to silence genes while minimizing potential side effects."

MDRNA researchers placed UNAs in the overhang positions of siRNAs, resulting in high RNAi potency with a substantial decrease in cytokine response. In addition, strategic placement of UNAs within the duplex region of an siRNA results in additional unique properties. For example, placement of UNA in the sense (passenger) strand eliminates sense strand off-targeting, and placement of UNA within the Dicer cut region of an siRNA blocks Dicer cleavage while maintaining potent RNAi activity.

Concurrently, MDRNA reported new information on its DiLA2 Platform research:

"Our proprietary DiLA2 Platform continues to demonstrate safe and effective delivery following repeat systemic dosing of up to 9 mg/kg of siRNA formulations in mice," commented Michael E. Houston, Ph.D., Vice President, Chemistry and Formulations. "We are very encouraged by the acute and repeat dose tolerability data of the DiLA2 Platform which affirm our belief that the DiLA2 Platform represents a significant advancement in the development of a novel formulation for improved siRNA delivery beyond the liver."

Data collected at 24 or 48 hours post-dose indicated that cell integrity is not compromised after a single dose of siRNA using the DiLA2 formulation. This included a dose-response of up to 9 mg/kg. Repeat dosing on an every-third-day schedule for two weeks further confirmed that DiLA2 liposomes are well tolerated, with no increase in blood markers of liver or kidney toxicity. Animal health (body weight, clinical signs, etc.) were consistent with the observation of no apparent toxicology. Of note: the highest doses in the single and repeat dose studies, 9 and 2 mg/kg, respectively, are well above the ED50 dose of > 0.5 mg/kg that MDRNA has previously reported as being highly effective with DiLA2 liposomes in the mouse ApoB model, and significantly higher than doses of liposomes historically associated with toxicity in vitro and in vivo.

"These results continue to demonstrate the breadth and depth of our RNAi-based drug discovery engine," said J. Michael French, President and CEO. "We can now add proprietary UNA-siRNA constructs to our existing IP portfolio of Dicer siRNA and meroduplex siRNA constructs. As part of our own pipeline and potential pharmaceutical R&D collaborations, we are able to offer multiple constructs as lead and back-up candidates. This is significant in the context that our 'back-up' candidates are not simply another sequence but an siRNA construct with unique characteristics in terms of both gene silencing and reduced off-target activity. Further, our DiLA2 Platform continues to demonstrate its versatility in its ability to systemically deliver any of these siRNA constructs in animal models. We feel that MDRNA is rapidly being recognized as having the critical mass necessary to make significant advances in the field of RNAi-based therapeutics."

About Unlocked Nucleic Acid

Unlocked Nucleic Acid (UNA) is an acyclic analog in which the bond between C2' and C3' atoms of what would otherwise be ribose is removed. This change in sugar structure renders this nucleic acid analog conformationally flexible. This characteristic is in sharp contrast to the widely used locked nucleosides that locks the sugar conformation by a bridged bond between C2' and C4' atoms. The flexible nature of UNA reduces the binding affinity between two strands of siRNA molecule and gives unique characteristics to its gene silencing abilities. MDRNA has demonstrated that UNA has the potential to improve siRNA therapeutics by increasing stability and reducing sense and antisense mediated off-target effects while retaining potency.

About the DiLA2 Platform

The DiLA2 Platform is MDRNA's proprietary platform for creating novel lipids from amino acids. The platform enables MDRNA to tailor the charge, linker and acyl chains in order to optimize the liposome for delivery to the target tissue of interest. In addition, the platform is designed to permit attachment of various peptides to improve a variety of delivery characteristics including nanoparticle formulation, cellular uptake, endosomal release and cell/tissue targeting.

About MDRNA, Inc.

MDRNA is a biotechnology company focused on the development and commercialization of therapeutic products based on RNA interference (RNAi). Our goal is to improve human health through the development of RNAi-based compounds and drug delivery technologies that together provide superior therapeutic options for patients. Over the past decade, we have developed substantial capabilities in molecular biology, cellular biology, lipid chemistry, peptide chemistry, pharmacology and bioinformatics, which we are applying to a wide range of RNAi technologies and delivery approaches. These capabilities plus the in-licensing of key RNAi-related intellectual property have rapidly enabled us to become a leading RNAi-based therapeutics company with a pre-clinical pipeline in key therapeutic areas including oncology, metabolic disorders and inflammation. Through our capabilities, expertise and know-how, we are incorporating multiple RNAi technologies as well as peptide- and lipid-based delivery approaches into a single integrated drug discovery platform that will be the engine for our clinical pipeline as well as a versatile platform for establishing broad therapeutic partnerships with biotechnology and pharmaceutical companies. We are also investing in new technologies that we expect to lead to safer and more effective RNAi-based therapeutics while aggressively building upon our broad and extensive intellectual property estate. By combining broad expertise in siRNA science with proven delivery platforms and a strong IP position, MDRNA is well positioned as a leading RNAi-based drug discovery and development company. Additional information about MDRNA, Inc. is available at http://www.mdrnainc.com.

MDRNA Forward-Looking Statement

Statements made in this news release may be forward-looking statements within the meaning of Federal Securities laws that are subject to certain risks and uncertainties and involve factors that may cause actual results to differ materially from those projected or suggested. Factors that could cause actual results to differ materially from those in forward-looking statements include, but are not limited to: (i) the ability of MDRNA or a subsidiary to obtain additional funding; (ii) the ability of MDRNA or a subsidiary to attract and/or maintain manufacturing, research, development and commercialization partners; (iii) the ability of MDRNA, a subsidiary and/or a partner to successfully complete product research and development, including preclinical and clinical studies and commercialization; (iv) the ability of MDRNA, a subsidiary and/or a partner to obtain required governmental approvals; and (v) the ability of MDRNA, a subsidiary and/or a partner to develop and commercialize products that can compete favorably with those of competitors. Additional factors that could cause actual results to differ materially from those projected or suggested in any forward-looking statements are contained in MDRNA's most recent periodic reports on Form 10-K and Form 10-Q that are filed with the Securities and Exchange Commission. MDRNA assumes no obligation to update and supplement forward-looking statements because of subsequent events.

Contact Information: Contact: Matthew D. Haines Senior Director, Investor Relations and Corporate Communications (212) 209-3874 McKinney|Chicago (Media) Alan Zachary (312) 944-6784 x 316 or (708) 707-6834