کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3355627 | 1217195 | 2012 | 12 صفحه PDF | دانلود رایگان |

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.
► Immune response by unmodified siRNAs is not length-, overhang- or design-dependent, but controlled by TLR7 and/or TLR8 immune stimulatory RNA motifs.
► A lack of TLR7 RNA motifs in the sense strand results in a loss of type I interferon secretion upon stimulation with the double stranded siRNA, even if the antisense strand contains a TLR7 motif.
► Using unmodified siRNA for both RNAi and immune response is limited to commercial available delivery systems: Dharmafect, HiPerfect and Superfect.
► The choice of an appropriate delivery system for siRNA and its correct N/P ratio can alter the immune response and RNAi of the siRNA, which should be tightly controlled.
► HiPerfect, Dharmafect and Superfect open potential new ways to develop dual functions for siRNAs: RNAi and activation of the immune system.
Journal: Immunology Letters - Volume 141, Issue 2, 30 January 2012, Pages 169–180