MDRNA Expands RNAi Bladder Cancer Program With The Vancouver Prostate Centre

Main Category: Cancer / Oncology
Also Included In: Urology / Nephrology
Article Date: 25 Nov 2009 - 7:00 PDT

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MDRNA, Inc. (NASDAQ: MRNA), a leading RNAi-based drug discovery and development company, today announced the extension and expansion of its collaboration with the Vancouver Prostate Centre (VPC), covering the discovery and development of RNAi-based therapeutics for the treatment of bladder cancer. Research conducted by scientists and surgeons from both institutions demonstrated that MDRNA's UsiRNA targeting human survivin and delivered via DiLA2 liposomes achieved up to 90% target knockdown in a mouse model of orthotopic bladder cancer. The effects of UsiRNA persisted for the duration of the three week study, and the level of survivin mRNA knockdown was associated with a significant reduction in tumor growth as measured by fluorescence from luciferase-expressing tumor cells.

"Intravesical delivery of the survivin UsiRNA using MDRNA's DiLA2 liposome formulation specifically targeted to a bladder tumor has yielded encouraging results that could lead to the development of useful therapies in patients with bladder cancer," said Dr. Alan So, an Assistant Professor in the Department of Urologic Sciences at the University of British Columbia, Research Scientist at the Vancouver Prostate Centre, and the study's principal investigator. "We are looking forward to expanding our current studies as the success of RNAi cancer therapeutics will be dependent upon the development of safe and efficacious delivery systems such as those being developed by MDRNA."

The collaboration with VPC's world-renowned clinical cancer research lab was formed in 2008 to investigate MDRNA's UsiRNAs and DiLA2 delivery platform in one of the Centre's well-validated bladder cancer models. The VPC is a National Centre of Excellence for translational research located at the University of British Columbia and the Vancouver General Hospital. In light of current results demonstrating efficient delivery and high potency for RNAi, the program will expand to evaluate UsiRNAs targeting other critical pathways in cancer, the impact on tumor biology, tumor growth, and survival rates. These studies are considered essential to identify the most effective target and dosing regimens for clinical intervention. MDRNA recently presented detailed results of the initial research at the International Society for Biological Therapy of Cancer.

"The encouraging data gathered so far supports our decision to add bladder cancer to our internal pipeline and provides further validation of the value of our RNAi drug discovery platform to potential pharmaceutical partners," said Dr. Barry Polisky, Chief Scientific Officer of MDRNA. "The expansion of this program reflects the value of VPC's world-class clinical research laboratory and the rewarding relationship that exists between MDRNA and VPC's outstanding scientific and medical teams. Together we are making progress to discover and develop novel treatments for this important unmet medical need."

About UsiRNAs and Unlocked Nucleobase Analogs

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.

Source
MDRNA, Inc.

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