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MDRNA Reports UsiRNA Reduces Tumor Growth In Vivo
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MDRNA, Inc. has 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, 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® (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."
In a presentation to BioPartnering Europe in London, 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® (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."
