Marina Biotech Demonstrates In Vivo Knockdown of a microRNA With a CRN-Modified Antagomir

BOTHELL, WA--(Marketwire - Aug 10, 2011) - Marina Biotech, Inc. (NASDAQ: MRNA), a leading RNA-based drug discovery and development company, reported in vivo data demonstrating up to 2.5-fold derepression of down-stream targets of a well-established microRNA, miR-122, with a Conformationally Restricted Nucleotide (CRN) modified antagonist. Derepression of down-stream targets represents the intended therapeutic benefit of inhibiting a specific microRNA controlling those targets; allowing the down-stream targets to express proteins which the microRNA typically down regulates. Thus, microRNA inhibition is one of the few therapeutic approaches that permits "upregulation" of specific gene targets. The CRN modified antagonist was highly effective at a dose of 10 mg/kg, while demonstrating good tolerability with repeat dosing.

"In vivo efficacy is a significant milestone in the advancement of our CRN technology and for our broad nucleic acid-based drug discovery platform," stated Barry Polisky, Ph.D., Chief Scientific Officer at Marina Biotech. "Success in establishing this drug discovery platform requires the capability to pursue both double-stranded and single-stranded oligonucleotide therapeutics. The work we've recently completed demonstrates that our proprietary CRN technology can increase the affinity of a single-stranded oligonucleotide to its intended target, whether it is a messenger RNA or microRNA. With our CRN and Unlocked Nucleobase Analog (UNA) technologies we have demonstrated that we can develop highly specific and potent double-stranded and single-stranded oligonucleotides. The combination of these unique chemistries and our multiple delivery technologies allows us to provide multiple nucleic acid-based approaches to our partners, and places us in a unique position within the field of nucleic acid-based therapeutics."

The identification and evaluation of microRNAs is one of the fastest growing fields in biology and medicine. MicroRNAs are considered to be key elements in maintaining normal cell physiology as microRNAs appear to be "central regulators of gene expression" that are critical for intra- and extra-cellular events. Thus, either the loss of specific microRNAs or the overexpression of specific microRNAs can lead to abnormal cell processes that are the underlying basis for disease. Inhibition of an aberrant microRNA with an antagonist, as demonstrated by the results present here, or the supplementation with a microRNA mimetic can restore the much needed balance between cellular communication pathways. Nucleic acid-based therapeutics are likely to be the most direct and efficient means of modulating the function of microRNAs, and are expected to provide much needed treatments of cancers and other diseases.

"With the completion of this early work with our CRN chemistry, we now have in vivo demonstration of our ability to develop single-stranded oligonucleotide therapeutic compounds," stated J. Michael French, President and CEO of Marina Biotech. "These results are the culmination of almost a year's effort in advancing the CRN technology. Further, we now have in vivo proof of concept across our entire nucleic acid-based therapeutic platform demonstrating the ability to silence gene targets through either RNA interference or translational blocking, or via a microRNA mimetic, and, in the case of these data, to up-regulate gene targets via a microRNA antagonist. I believe we have put together the broadest nucleic acid-based drug discovery engine in the industry and a one-of-a-kind platform upon which to build pharma partnerships."

About Conformationally Restricted Nucleotides

Conformationally Restricted Nucleotides are analogs in which a chemical bridge connects the C2' and C4' carbons of ribose. Ribose, a five-carbon ring-like structure, forms the central region of a nucleotide (comprised of a nucleobase, ribose, and phosphate group). The chemical bridge in the ribose of a CRN locks the ribose in a fixed position, which in turn restricts the flexibility of the nucleobase and phosphate group. Substitution of a CRN within an RNA- or DNA-based oligonucleotide has the advantages of increased hybridization affinity and enhanced resistance to nuclease degradation. CRN technology provides a direct means of developing highly potent and specific nucleic acid-based therapeutics to target messenger RNAs or microRNAs. These targets represent disease pathways that are typically "undruggable" or "difficult to target" by small molecule or monoclonal antibodies, and are appropriate for disease areas with significant unmet needs, such as inflammation, metabolic disease, and cancers. The CRN patent estate consists of two issued patents broadly covering CRN compounds and CRN containing oligonucleotides, and one pending patent application covering additional applications of CRNs.

About Marina Biotech, Inc.

Marina Biotech is a biotechnology company, focused on the development and commercialization of RNA interference- (RNAi) and RNA-based therapeutics. The Marina Biotech pipeline currently includes a clinical program in Familial Adenomatous Polyposis (a precancerous syndrome) and two preclinical programs -- in bladder cancer and malignant ascites. Marina Biotech entered into an exclusive agreement with Debiopharm Group for the development and commercialization of the bladder cancer program. Marina Biotech's goal is to improve human health through the development of RNAi and RNA-based compounds and drug delivery technologies that together provide superior therapeutic options for patients. Additional information about Marina Biotech is available at http://www.marinabio.com.

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 Marina Biotech to obtain additional funding; (ii) the ability of Marina Biotech to attract and/or maintain manufacturing, research, development and commercialization partners; (iii) the ability of Marina Biotech and/or a partner to successfully complete product research and development, including preclinical and clinical studies and commercialization; (iv) the ability of Marina Biotech and/or a partner to obtain required governmental approvals; and (v) the ability of Marina Biotech 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 Marina Biotech's most recent periodic reports on Form 10-K and Form 10-Q that are filed with the Securities and Exchange Commission. Marina Biotech assumes no obligation to update and supplement forward-looking statements because of subsequent events.