MDRNA, Inc. Demonstrates In Vivo Efficacy with Proprietary DiLA² Delivery Platform

BOTHELL, Wash.--(BUSINESS WIRE)--

MDRNA, Inc. (Nasdaq: MRNA) announced today positive in vivo efficacy data using a novel combination of a meroduplex siRNA and MDRNA’s proprietary lipid-based delivery platform, the DiLA² Platform. The data presented today by Narendra Vaish, Ph.D., MBA, Senior Research Scientist and Group Leader - RNAi Platform Technologies at “RNA 2008,” the 13^th Annual Meeting of the RNA Society in Berlin, Germany, indicate that a single iv administration of MDRNA meroduplexes targeting apolipoprotein B mRNA formulated in a DiLA² delivery vehicle showed robust activity in a mouse model. The meroduplex siRNA decreased both ApoB mRNA and serum cholesterol levels. In addition, the formulated, chemically modified siRNA resulted in minimal body weight loss in mice while showing reduced levels of cytokine stimulation.

“We are pleased to report continued progress in the development of siRNA approaches to gene down regulation as well as an extensive lipid-based delivery platform, the DiLA² Platform,” stated Michael Houston, Ph.D., Vice President of Chemistry and Formulations. “The results of this pre-clinical work suggest that a unique combination of both a novel siRNA construct within a lipid-based delivery formulation has the potential to elicit a potent RNAi response and reduce off-target activity. We believe that a drug discovery platform that has multiple approaches to activating the RNAi process, as well as a broad delivery capability able to target multiple tissue systems, is necessary to successfully develop RNAi-based therapeutics across all human diseases.”

About Meroduplexes

One of the intermediate steps in RNA interference involves the loading of small, double-stranded RNA duplexes (siRNAs) into the RNA Induced Silencing Complex, or RISC. Either strand of the siRNA duplex can assemble into the active RISC complex, and only one strand of the siRNA duplex is incorporated into the RISC while the other strand is degraded and removed. It has been generally accepted that a continuous siRNA duplex is required for efficient RISC assembly. However, MDRNA has shown that siRNAs containing a nick or gap in the sense strand can also be extremely active in RNAi. MDRNA has called these constructs “meroduplexes” to highlight segmented nature of the siRNA duplex. The use of these types of siRNA constructs should help eliminate the off-target potential of the sense strand by preventing its loading into RISC.

Meroduplexes show surprising flexibility in their design. Activity is maintained with a nick at almost any position along the siRNA sense strand - as long as the two fragments of the nicked sense strand retain sufficient base-pairing free energy to form the duplex. In addition, gaps in the sense strand of up to five nucleotides still support RNAi; both RISC and Dicer substrate meroduplex constructs are active. This discovery should help eliminate the off-target potential of the sense strand by preventing its loading into RISC for use as a full-length guide strand, and help elucidate the mechanism of RISC loading and sense strand removal.

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 such that the properties of the liposome are optimized for delivery to the target tissue of interest. In addition, the platform is amenable to attachment of targeting moieties for improved delivery specificity.

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.