The latest news from academia, regulators
research labs and other things of interest
Posted: June 8, 2009
MDRNA Reports Demonstration of Effective Localized Delivery of a UsiRNA to a Solid Tumor
(Nanowerk News) MDRNA, Inc. announced today in vivo data from a bladder cancer model demonstrating effective localized delivery of a UsiRNA to a solid tumor, thus further expanding the delivery capabilities of the DiLA2 Platform. In addition, the Company reported in vivo data demonstrating the ability of its proprietary peptide-based nanoparticle technology to significantly improve siRNA delivery efficiency.
The integration of the peptide nanoparticle technology with the DiLA2 Platform resulted in 85% knockdown of ApoB messenger RNA while decreasing the overall amount of the DiLA2 delivery vehicle by 45%. The data are being presented today at the RNA Interference Summit in San Francisco by Roger Adami, Ph.D., Associate Director, Molecular Pharmaceutics, MDRNA, Inc.
Dr. Adami will also present data demonstrating knockdown of additional hepatocyte targets in rodent models. The DiLA2 liposomes showed 90% knockdown of DGAT2 in mice following a single 2 mg/kg administration and a 75% knockdown of PCSK9 with a single 2 mg/kg dose. This highly efficient delivery to hepatocytes provides the basis for MDRNA's development pipeline in oncology.
"The data reported today demonstrate the breadth and versatility of the DiLA2 delivery system," stated Barry Polisky, Ph.D., Chief Scientific Officer. "We believe that the DiLA2 Platform will enable effective therapeutic applications of siRNAs in oncology and various other disease indications. Additionally, peptide-siRNA particles combined with the DiLA2 Platform will provide improved delivery efficiency of RNAi-based therapeutics. During 2009, we intend to expand the capabilities of the DiLA2 delivery system to target multiple oncology indications beyond our initial internal program in liver cancer."
UsiRNAs are duplex siRNAs that are modified with non-nucleotide acyclic monomers, termed unlocked nucleobase analogs (UNA), in which the bond between two adjacent carbon atoms of ribose is removed. UsiRNAs are fully recognized by the RNAi machinery and provide for potent RNAi activity.
Placement of UNA within a UsiRNA minimizes the potential for off-target effects by the guide strand as well as undesired activity of the passenger strand. Further, the change in sugar structure renders this unlocked nucleobase analog conformationally flexible. The flexibility of the monomer escapes the body's surveillance mechanisms associated with cytokine induction, as well as providing protection from nuclease degradation.
About the DiLA2 Platform
The DiLA2 Platform is MDRNA's proprietary platform for creating novel liposomal delivery systems from amino acids. The platform enables MDRNA to tailor the charge, linker and acyl chains of amino acids in order to optimize the liposome for delivery to the target tissue of interest and is designed to permit attachment of various peptides and other targeting molecules to improve a variety of delivery characteristics. In addition, MDRNA is utilizing peptides for nanoparticle formulations to increase cellular uptake and endosomal release.