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MDRNA Demonstrates Significantly Reduced Off-Target Activity for RNAi-Based Compounds
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MDRNA Demonstrates Significantly Reduced Off-Target Activity for RNAi-Based Compounds

MDRNA Demonstrates Significantly Reduced Off-Target Activity for RNAi-Based Compounds
News

MDRNA Demonstrates Significantly Reduced Off-Target Activity for RNAi-Based Compounds

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MDRNA, Inc. announces the presentation of data highlighting the ability of the UsiRNA construct to significantly minimize off-target effects while maintaining potent RNA Interference (RNAi) activity.

Narendra Vaish, Ph.D., MBA, Associate Director, Discovery Research and Pharmaceutical Development, presented the data at the Keystone Symposia on "RNA Silencing: Mechanism, Biology and Application" from January 14 to 19, 2010, Keystone Resort, Keystone, Colorado.

UsiRNAs are MDRNA's proprietary constructs in which Unlocked Nucleobase Analogs (UNA) strategically replace ribonucleobases. Placement of UNA in the passenger strand specifically blocks the activity of this strand to function in RNAi, thus decreasing off-target activity. Placement of UNA within the guide strand confers greater specificity upon RNAi by inhibiting micro-RNA-like effects.

Using microarray analysis to simultaneously measure the expression levels of more than 30,000 genes, a UNA in the passenger strand reduced the off-target effects by greater than two-fold as compared to a standard siRNA. More importantly, a UsiRNA, with both passenger and guide strand UNA placements reduced the off-targets effects by more than 10-fold compared to a standard siRNA.

MDRNA also reported delivery of UsiRNA against Survivin and PLK-1, by MDRNA's proprietary DiLA2-based liposome formulations via systemic (liver cancer) or local (bladder cancer) administration, and demonstrated potent and persistent target knock-down and inhibition of tumor growth. Significant knockdown in the expression level of a liver gene has also been described in non-human primates following intravenous (systemic) administration of a UsiRNA using DiLA2 liposomes.

"These new data highlight the ability of our UsiRNA construct to inhibit passenger strand activity and achieve greater guide strand specificity," said Dr. Barry Polisky, Chief Scientific Officer of MDRNA. "These advantages are reflected in the microarray data which indicate UsiRNAs mitigate off-target effects that can occur in RNAi. The inhibition of non-cancer, and cancer targets in two divergent models via different routes of administration, demonstrates the strength of pairing the UsiRNA and DiLA2 delivery platforms for the development of RNAi-based therapeutics."
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