Data Generated Under an Early Collaborative Effort Demonstrated Abrogation of Cytotoxicity Associated With microRNA-Like Off-Targeting by Substituting a Single Unlocked Nucleobase Analog (UNA) Moiety in the Guide Strand of an siRNA (UsiRNA)
BOTHELL, WA, Nov 02, 2011 (MARKETWIRE via COMTEX) -- Marina Biotech, Inc. (NASDAQ: MRNA), a leading oligonucleotide-based drug discovery and development company, reported significant reduction of microRNA-like cytotoxic effect by incorporating a single UNA moiety in the guide strand of an siRNA when compared to an unmodified siRNA of the same sequence. The data was generated under one of the Company's early collaborative efforts. Unmodified siRNAs can induce unintended effects, including cytotoxicity, which can lead to safety issues. Substitution with a single UNA in the seed region of the siRNA guide strand resulted in abrogation of cell death/anti-proliferation effects associated with a specific siRNA preclinical candidate for which unintended microRNA targets had already been identified.
"These results further confirm the utility and breadth of our UNA technology in mitigating an undesirable effect associated with unmodified siRNAs," stated Richard T. Ho, M.D.-Ph.D., Executive Vice President, Research and Development at Marina Biotech, Inc. "This work confirms our experience that the majority of unintended microRNA related off-target events are likely to be reduced by placing a UNA in the seed region of the siRNA guide strand. The ability to "rescue" a highly active siRNA by dramatically reducing its cytotoxic effects with a single UNA substitution emphasizes the advantages of the UNA technology and the UsiRNA platform in the development of oligonucleotide therapeutics which capitalize on the power of the RNAi pathway."
UNA are non-nucleotide, acyclic monomers which provide greater structural flexibility in an oligonucleotide strand. Marina Biotech's proprietary UsiRNA constructs are siRNA incorporating at least one UNA and are distinct from the standard siRNA constructs used by others in the industry. UsiRNAs are specifically designed to provide greater specificity for RNAi-based therapeutics. Substitution with UNA in the passenger strand (non-targeting strand) is intended to eliminate its participation in the RNAi process. Substitution in the guide strand (targeting strand) is intended to eliminate miRNA-like events, while preserving high siRNA-like activity. Optimization of UNA substitutions in siRNA has previously been published by Marina Biotech (Nucleic Acids Res. 2011 Mar;39(5):1823-32.).
About Marina Biotech, Inc.
Marina Biotech is a biotechnology company, focused on the development and commercialization of oligonucleotide-based therapeutics utilizing multiple mechanisms of action including RNA interference (RNAi) and messenger RNA translational blocking. 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 oligonucleotide-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.
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.
Marina Biotech, Inc.
Interim Chief Financial Officer
SOURCE: Marina Biotech, Inc.