May 06, 2010 08:00 ET

MDRNA, Inc. Reports Novel Target Specificity Characteristics of Its Proprietary UsiRNA Technology for RNAi-based Therapeutics

UNA Technology Provides Essential Drug-Like Properties to RNAi-Based Therapeutics

BOTHELL, WA--(Marketwire - May 6, 2010) -  MDRNA, Inc. (NASDAQ: MRNA), a leading RNAi-based drug discovery and development company, today reported on advances made with the Company's proprietary UsiRNA construct for RNA interference (RNAi). The term UsiRNA denotes inclusion of unlocked nucleobase analogs (UNA) in the double-stranded oligonucleotide construct. UsiRNAs demonstrate enhanced specificity and efficacy in comparison to standard siRNAs. Today's data add to previously reported data on microarray analysis indicating the UsiRNA construct not only significantly eliminates off-target events, but does so with no apparent new off-target silencing. That is, UNA's improve the efficacy of the siRNA construct without further off-target activity related to the UNA chemistry. The data were presented by Narendra Vaish, Ph.D., MBA, Associate Director, Discovery Research and Pharmaceutical Development, at the "RNAi and miRNA World Congress" in Boston, MA.

RNAi provides a means to target a specific mRNA and this "on-target" precision is a key advantage for RNAi-based therapeutics. However, the potential exists for "off-target" effects with standard siRNAs via the non-targeting strand (e.g., passenger strand) or unintended interactions associated with the targeting strand (e.g. guide strand). The UsiRNA construct was designed to directly address these concerns. Substitution in the passenger strand is intended to eliminate its participation in the RNAi process. Substitution in the guide strand is intended to eliminate miRNA-like events, while preserving siRNA-like activity. Furthermore, as described previously, UsiRNAs have a lower potential for cytokine induction that can occur with standard siRNAs, and the absence of alterations in cytokine related genes are likely a part of the overall reduction in the off-target events.

Activity evaluation and microarray analysis confirmed the advantages of UsiRNAs. Compared to the standard siRNA format, elimination of passenger strand activity was achieved with UNA substitution. Guide strand substitution with UNA retained intended siRNA-like activity but demonstrated no miRNA-like activity. Microarray analysis revealed significant change in the expression of 389 genes with the standard siRNA format. In contrast, UsiRNA altered expression of only 35 genes, a greater than 90% reduction in off-target events with no apparent new off-target silencing.

"These new data highlight the ability of our UsiRNA construct to achieve highly specific inhibition while mitigating the off-target effects that can occur with standard siRNAs," said Dr. Barry Polisky, Chief Scientific Officer of MDRNA. "The inhibition of target mRNA in our bladder cancer model, demonstrates the strength of pairing the UsiRNA construct and DiLA2 delivery platforms for the development of RNAi-based therapeutics."

About MDRNA's Technology

MDRNA has a broad intellectual property estate that encompasses four key RNAi technology platforms: siRNA constructs, chemistry, nucleic acid delivery, and gene targets. The MDRNA-owned siRNA constructs and chemistry include its proprietary UsiRNA construct, which is a duplex siRNA in which non-nucleotide acyclic monomers (UNAs) have been included, and is distinct from the standard siRNA construct used by others in the industry. UsiRNAs are fully recognized by the RNAi machinery and provide for potent RNAi activity while specific placement of UNAs in a duplex siRNA minimizes potential off-target effects by the guide strand and reduces undesired passenger strand activity. Furthermore, UsiRNAs escape the surveillance mechanisms associated with cytokine induction, and provide protection from nuclease degradation.

The MDRNA delivery platforms include DiLA2 and nanoparticle forming peptides. DiLA2 is an MDRNA proprietary delivery platform of novel synthetic di-alkylated amino acid compounds used to make liposomal delivery formulations. The DiLA2 platform enables MDRNA to tailor the charge, linker and acyl chains of amino acids in order to configure liposomes for delivery to target tissues 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. The MDRNA peptide nanoparticle platform includes exclusively in-licensed and developed IP surrounding the use of peptides for nanoparticle formulations that increase cellular uptake and endosomal release of siRNAs. MDRNA is currently biopanning its patented phage display library to identify additional peptides for targeted delivery, cellular uptake and endosomal release of siRNA.

MDRNA owns or controls 17 issued or allowed patents, and has 41 pending patent applications, 134 pending foreign patent applications and 6 PCT applications.

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 oncology. 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

MDRNA Forward-Looking Statements

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 to obtain additional funding; (ii) the ability of MDRNA to attract and/or maintain manufacturing, research, development and commercialization partners; (iii) the ability of MDRNA and/or a partner to successfully complete product research and development, including preclinical and clinical studies and commercialization; (iv) the ability of MDRNA and/or a partner to obtain required governmental approvals; (v) the ability of MDRNA and/or a partner to develop and commercialize products that can compete favorably with those of competitors; and (vi) the failure of the stockholders of MDRNA to approve the merger with Cequent, the failure of either party to meet any of the other conditions to closing the merger, contractual restrictions on the conduct of our business included in the merger agreement, and any impact on our relationships with third parties as a result of the announcement of the proposed merger. 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