MDRNA Reports UsiRNA Reduces Tumor Growth In Vivo
- Category: DNA RNA and Cells
- Published on Monday, 12 October 2009 03:00
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Demonstrates RNAi-Mediated Knockdown of Previously "Non-Druggable" Targets in Liver and Bladder Cancers
BOTHELL, WA, USA | October 12, 2009 | MDRNA, Inc. (NASDAQ: MRNA), a leading RNAi-based drug discovery and development company, today presented new in vivo data demonstrating continued progress in the advancement of the Company's oncology program. J. Michael French, President and CEO, reported that MDRNA's UsiRNAs, delivered by the Company's DiLA2 platform, down-regulated a previously "non-druggable" target with subsequent reductions in tumor growth in models of liver and bladder cancer via both systemic and local delivery.
In a presentation to BioPartnering Europe in London today, Mr. French said that MDRNA has demonstrated successful delivery of a UsiRNA targeting survivin, a protein involved in mitotic progression and inhibition of apoptosis, via intravenous administration using its DiLA2 liposome formulation in two liver cancer models. Knockdown ( > 60%) of survivin mRNA in a rodent orthotopic model was noted as early as 24 hours after a second (of six) dose and this was associated with an approximate 65% decrease in tumor weight at study termination; this decrease was comparable to tumor weight reduction with Avastin(R) (bevacizumab)-treated mice as a positive control. A similar level of survivin mRNA knockdown was noted in subcutaneously implanted liver tumors following intravenous administration of the UsiRNA/DiLA2 liposomes.
Data from an orthotopic bladder cancer model were also presented, in which localized application (intravesical dosing) of the survivin UsiRNA to a bladder tumor was performed using a DiLA2 liposome formulation. Again, the UsiRNA was highly active in providing gene silencing, demonstrating > 90% inhibition of survivin mRNA which was dose-dependent and sustained over at least a three week period. At study termination there was also a dose-dependent decrease in bioluminescence of up to approximately 90% in UsiRNA-treated mice which is a clear indication of reduced tumor growth.
Mr. French said, "We have always maintained that our RNAi discovery engine can generate novel compounds with broad therapeutic applicability. These data are a powerful indicator of the value and strength of that drug discovery platform and represents a significant step in the advancement of our product pipeline. Moreover, we now have evidence illustrating the potential role of RNAi-based therapeutics in down-regulating typically 'non-druggable' targets."
The presentation given by Mr. French is posted on the Company website (www.mdrnainc.com).
A UsiRNA is a duplex siRNA containing at least one Unlocked Nucleobase Analog (UNA). In a UsiRNA, UNAs are non-nucleotide monomers and synthesized much like RNA in the construction of a double-stranded oligonucelotide for use as an RNAi-based therapeutic. In the case of the UsiRNA, UNA is substituted for specific nucleotides in both the guide and passenger strands. UsiRNAs are fully recognized by the cellular RNAi machinery, as demonstrated by their potent activity. MDRNA has also shown that substitution of UNA for specific RNA increases stability to nucleases, substantially reduces cytokine induction, and reduces passenger and guide strand-mediated offtarget effects. The high potency, and improved drug-like properties, associated with UsiRNAs provide the potential to greatly enhance RNAi-based therapeutics.
About the DiLA2 Delivery Platform
The DiLA2 Delivery Platform is MDRNA's proprietary platform for creating novel liposomal delivery systems based on di-alkylated amino acids (DiLA2). The DiLA2 Platform enables MDRNA to tailor the charge, linker length, and acyl chain characteristics to improve delivery of the liposomes to target tissue of interest. In vivo studies have demonstrated effective delivery in models of metabolic disease, cancer, and other diseases. DiLA2-based liposomes are well tolerated for repeat dose, and systemic and local administration. MDRNA is also utilizing condensing peptides to form peptide-siRNA nanoparticles to further increase the delivery efficiency of its DiLA2 delivery systems. In addition, the platform is designed to permit attachment of peptides and other targeting molecules for delivery to a variety of tissues, and thus provide for a diverse therapeutic portfolio.
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 http://www.mdrnainc.com.
SOURCE: MDRNA, Inc.