Systemic delivery of 3-stranded siRNA constructs formulated in
proprietary liposomes decreases serum cholesterol
MDRNA, Inc. (Nasdaq: MRNA) announced today positive in vivo
efficacy data using a novel combination of a meroduplex siRNA and MDRNA’s
proprietary lipid-based delivery platform, the DiLA2
Platform. The data presented today by Narendra Vaish, Ph.D., MBA, Senior
Research Scientist and Group Leader - RNAi Platform Technologies at “RNA
2008,” the 13th
Annual Meeting of the RNA Society in Berlin, Germany, indicate that a
single iv administration of MDRNA meroduplexes targeting apolipoprotein
B mRNA formulated in a DiLA2 delivery vehicle
showed robust activity in a mouse model. The meroduplex siRNA decreased
both ApoB mRNA and serum cholesterol levels. In addition, the
formulated, chemically modified siRNA resulted in minimal body weight
loss in mice while showing reduced levels of cytokine stimulation.
“We are pleased to report continued progress
in the development of siRNA approaches to gene down regulation as well
as an extensive lipid-based delivery platform, the DiLA2
Platform,” stated Michael Houston, Ph.D., Vice
President of Chemistry and Formulations. “The
results of this pre-clinical work suggest that a unique combination of
both a novel siRNA construct within a lipid-based delivery formulation
has the potential to elicit a potent RNAi response and reduce off-target
activity. We believe that a drug discovery platform that has multiple
approaches to activating the RNAi process, as well as a broad delivery
capability able to target multiple tissue systems, is necessary to
successfully develop RNAi-based therapeutics across all human diseases.”
About Meroduplexes
One of the intermediate steps in RNA interference involves the loading
of small, double-stranded RNA duplexes (siRNAs) into the RNA Induced
Silencing Complex, or RISC. Either strand of the siRNA duplex can
assemble into the active RISC complex, and only one strand of the siRNA
duplex is incorporated into the RISC while the other strand is degraded
and removed. It has been generally accepted that a continuous siRNA
duplex is required for efficient RISC assembly. However, MDRNA has shown
that siRNAs containing a nick or gap in the sense strand can also be
extremely active in RNAi. MDRNA has called these constructs “meroduplexes”
to highlight segmented nature of the siRNA duplex.
