MDRNA Successfully Silences Gene Targets in Animal Models Using Novel UsiRNA Constructs

BOTHELL, WA--(Marketwire - February 23, 2009) - MDRNA, Inc. (NASDAQ: MRNA) announced today positive in vivo efficacy data on its proprietary UsiRNA constructs demonstrating a dose response which resulted in up to 90% knockdown of ApoB message in a rodent model. The data were presented by Michael V. Templin, Ph.D., Vice President, Discovery Research and Pharmaceutical Development of MDRNA, at the inaugural Informa Life Sciences TIDES Oligonucleotide and Peptide® Research, Technology and Product Development Conference in Tokyo, Japan.

"Our UsiRNA constructs offer a novel and proprietary means of providing highly potent siRNAs while increasing specificity," stated Barry Polisky, Ph.D., Chief Scientific Officer of MDRNA. "UsiRNAs were highly active in the mouse ApoB model for both message inhibition and serum cholesterol reduction. In these cases, UsiRNAs were fully compatible with RNAi machinery yet showed a substantial decrease in cytokine response. We are encouraged by these significant results and believe we have a unique siRNA construct to silence genes while minimizing potential side effects."

UsiRNAs are duplex siRNAs that are modified with non-nucleotide acyclic monomers, termed unlocked nucleobase analogs (UNA), in which the bond between two adjacent carbon atoms of ribose is removed. UsiRNAs are fully recognized by the RNAi machinery and provide for potent RNAi activity. Placement of UNA within UsiRNA minimizes the potential for off-target effects by the guide strand as well as undesired activity of the passenger strand. Further, the change in sugar structure renders this unlocked nucleobase analog conformationally flexible. The flexibility of the monomer escapes the surveillance mechanisms associated with cytokine induction, as well as providing protection from nuclease degradation.

MDRNA also reported new information on its DiLA2 Platform delivery technology:

"We are pleased to announce that our proprietary DiLA2 Platform achieved knockdown of two additional genes in liver tissue, DGAT2 and PCSK9, that are potentially important therapeutic targets, and the Platform continues to demonstrate safe and effective delivery following repeat systemic dosing of up to 9 mg/kg of siRNA formulations in mice," added Dr. Polisky. "The acute and repeat dose tolerability data of the DiLA2 Platform are promising. Repeat dosing on an every-third-day schedule for two weeks further indicates that DiLA2 liposomes are well tolerated. Our ability to deliver siRNAs to hepatocytes while achieving knockdown of multiple gene targets affirms our belief that the DiLA2 Platform represents a significant advancement in the development of a novel formulation for improved siRNA delivery."

"Our proprietary and novel UsiRNA constructs -- highly active siRNAs which minimize off-target activity -- represent a potential major step forward in the development of RNAi-based therapeutics," stated J. Michael French, President and Chief Executive Officer of MDRNA. "Further, our DiLA2 Platform continues to demonstrate its versatility in its ability to safely and efficiently deliver siRNAs against multiple gene targets and effectively silence those genes. The results reported today represent a further demonstration of the breadth and depth of our RNAi-based drug discovery engine and the capability and expertise of our scientific team."

About the DiLA2 Platform

The DiLA2 Platform is MDRNA's proprietary platform for creating novel liposomal delivery systems from amino acids. The platform enables MDRNA to tailor the charge, linker and acyl chains of amino acids 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 and other targeting molecules to improve a variety of delivery characteristics. In addition, MDRNA is utilizing peptides for nanoparticle formulations to increase cellular uptake and endosomal release.

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 by combining novel RNAi-based compounds and proprietary peptide- and liposomal-based drug delivery technologies to provide superior therapeutic options. Our multi-disciplinary portfolio of capabilities includes molecular biology, cellular biology, formulation expertise, peptide and alkylated amino acid chemistry, pharmacology, toxicology and bioinformatics. We are applying this expertise to a single, integrated drug discovery platform that will be the engine for our clinical pipeline and a versatile platform for establishing broad therapeutic partnerships. We are also building on new technologies, such as UsiRNAs that incorporate the non-nucleotide moiety Unlocked Nucleobase Analog (UNA) within the siRNA molecule, that we expect to lead to safer and more effective RNAi-based therapeutics. By combining broad expertise in siRNA science with proven delivery platforms and a strong and growing IP position, MDRNA is well positioned as a leading RNAi therapeutics company and value-added collaborator for our research partners. 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