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Updated: May 28, 2026

Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy
Published on: September 5, 2016
Impact of delivery systems on siRNA immune activation and RNA interference
Alexandra Forsbach1, Christian Müller, Carmen Montino
1Coley Pharmaceutical GmbH, Merowingerplatz 1a, 402254 Düsseldorf, Germany. aforsbach@gmx.de
Abstract:
Small interfering RNAs (siRNAs) induce robust degradation of homologous mRNAs. Highly specific silencing of target genes makes siRNA an interesting tool in drug development. However, several non-specific effects complicate the use of RNA interference (RNAi). One of the most prevalent unspecific effects is triggering the innate immune system in mammals. In parallel, activating the immune system may open the possibility to develop dual siRNAs for treatment of a variety of diseases including cancer. Here, we show that the best use of unmodified siRNAs for RNAi and immune activation depends on the delivery system, formulation condition, sequence and siRNA design concerning ORN motifs. Testing several commercial delivery systems identified that the optimal siRNAs for dual functions should contain TLR7/8 ORN motifs at least in the antisense strand and be delivered by either Dharmafect or HiPerfect. Superfect delivery system only activates TLR7 and opens new capabilities in RNAi and immune activation.
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