Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA

By A. Judge, Vandana Sood, J. Shaw, D. Fang, K. Mcclintock, I. Maclachlan. Nature Biotechnology, 2005

1,251 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c13e007a290c2bdd8f7fcff6cc11d0e982dc89f8

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In Cancer Research

In Molecular Biology

Citations in the corpus

In vivo delivery of miRNAs for cancer therapy: Challenges and strategies (2014, background): “These TLRs sensing dsRNA molecules in cellular endosomal and lysosomal compartments stimulate the type I interferon (IFN) pathway and trigger cytokine production according to the structure, sequence, and the delivery system [70,71].”
Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application (2010, background): “Early experiments exploring the effects of siRNAs on immune stimulation showed that siRNAs could activate cells of the immune system and induce the production of cytokines in vivo and in vitro”
Knocking down barriers: advances in siRNA delivery (2009, background): “For example, many non-modified siRNAs can induce nonspecific activation of the immune system through the Toll-like receptor 7 (TlR7) pathway 38, 39 .”
RNA interference in the clinic: challenges and future directions (2010, background): “For example, uridine- and guanosine-rich sequences with either UG dinucleotide or 5′-UGU-3′ motifs potently activate TLR7 and TLR8, and avoidance of such sequences decreases this respons”
Strategies for silencing human disease using RNA interference (2007, background): “These TLRs serve as pattern-recognition sensors of specific immunostimulatory sequence motifs that should be avoided in siRNA design (that is, 5′-GUCCUUCAA-3′ and 5′-UGUGU-3′”
In vivo imaging of siRNA delivery and silencing in tumors (2007, background): “A major concern related to the in vivo delivery of siRNAs deals with the induction of type I interferon and inflammatory cytokine”
Innovative approaches for cancer treatment: current perspectives and new challenges (2019, background): “Occasionally, they can induce off-target effects [178] or elicit innate immune responses, followed by specific inflammation [179, 180].”
RNAi-Based Insecticidal Crops: Potential Effects on Nontarget Species (2013, background): “This specificity is related to the physiological conditions of the insect gut, especially the presence of specific receptor sites on the midgut epithelium (van Frankenhuyzen 2009, Jurat-Fuentes and Jackson 2012).”
Lipid-based Nanoparticles for Nucleic Acid Delivery (2007, background): “investigated the antibody response to PEGylated liposomes (56) and sequence-dependent innate immune response to siRNA (10), which raises a concern on the immune response of PEG-lipid-based NP particularly when multiple doses are needed to treat the disease.”
RNAi therapeutics: a potential new class of pharmaceutical drugs (2006, background): “Evidence supporting the latter approach comes from studies in which chemical modifications at the 2′ position of nucleotides within putative TLR-7-interacting sequences eliminate immune stimulation without compromising silencing activity 36, 39 .”
Lipid-like materials for low-dose, in vivo gene silencing (2010, background): “The most significant challenges to delivery include the relatively large size (∼13 kDa) and negative charge of siRNA molecules as well as their susceptibility to enzymatic degradation in vivo (4, 5).”
Interfering with disease: a progress report on siRNA-based therapeutics (2007, background): “Candidate duplexes can be transfected into plasmacytoid dendritic cells to test whether they induce interferon expression 27, 28 ; those that do can be discarded.”