Impact of delivery systems on siRNA immune activation and RNA interference

Highlights ► 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 strande...

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Bibliographic Details
Published in:Immunology letters 2012-01, Vol.141 (2), p.169-180
Main Authors: Forsbach, Alexandra, Müller, Christian, Montino, Carmen, Kritzler, Andrea, Curdt, Rainer, Benahmed, Amina, Jurk, Marion, Vollmer, Jörg
Format: Article
Language:English
Subjects:
Allergy and Immunology
Antisense
Base Sequence
Cancer
Cell Line
Combination RNAi and immune activation
Cytokines - metabolism
Delivery systems
Drug development
Gene silencing
Genetic Vectors
Humans
Immune response
Immune system
Immunity, Innate - genetics
Immunization - methods
Leukocytes, Mononuclear - immunology
Leukocytes, Mononuclear - metabolism
Leukocytes, Mononuclear - pathology
Molecular Sequence Data
mRNA
NF-kappa B - genetics
NF-kappa B - metabolism
Nucleotide Motifs - genetics
RNA Interference
RNA, Small Interfering - genetics
RNA-mediated interference
siRNA
TLR7 protein
Toll-Like Receptor 7 - genetics
Toll-Like Receptor 8 - genetics
Toll-like receptors
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Summary:Highlights ► 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.
ISSN:0165-2478
1879-0542
DOI:10.1016/j.imlet.2011.10.001