Expression profiling reveals off-target gene regulation by RNAi

By A. Jackson, S. Bartz, Janell M. Schelter, Sumire V. Kobayashi, J. Burchard, M. Mao, Bin Li, G. Cavet, Peter S. Linsley. 2003

2,462 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology

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Citations in the corpus

Causal inference by using invariant prediction: identification and confidence intervals (2015, background): “As an example we mention gene knockout experiments with off-target effects in biology (e.g. Jackson et al. (2003) and Kulkarni et al. (2006)).”
MicroRNA targets in Drosophila (2003, neutral): “Intriguingly though, siRNAguided cleavage activity can be detected with sometimes distantly-related complementary sequences when siRNA specificity is evaluated at a genome-wide level [38].”
Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. (2005, background): “An analysis of gene expression profiling suggested that RNA down-regulation might occur with as few as 11 complementary base pairs within the 21-bp siRNA sequence (44).”
MicroRNA targeting specificity in mammals: determinants beyond seed pairing. (2007, methodology): “changes in mRNA levels after siRNA transfection (Jackson et al. 2003) after first predicting the top and bottom quartiles using context scores calculated as in (D) for messages with single 7mer-m8 sites to the siRNAs (Figure S5); otherwise as shown for Figure 1B (p < 10 (31), two-sided KS test, comp”
ADAM10 is the physiologically relevant, constitutive α‐secretase of the amyloid precursor protein in primary neurons (2010, background): “…VOL 29 | NO 17 | 2010 &2010 European Molecular Biology Organization3028 et al, 2009), it seems possible that earlier conclusions about ADAM9 and 17 as APP a-secretase may have been due to offtarget effects (Jackson et al, 2003), but not due to the specific reduction of ADAM protease expression.”
Identification of the gene for vitamin K epoxide reductase (2004, background): “To minimize the potential for off-target silencing effects, only those sequence targets with more than three mismatches against unrelated sequences were selecte”
Illuminating the silence: understanding the structure and function of small RNAs (2007, background): “Second, chemical modifications could influence specific steps of RISC function and possibly reduce off-target effects of RNAi that arise from partial complementarity between the guide and target-mRNA strand”
Transcripts Targeted by the MicroRNA-16 Family Cooperatively Regulate Cell Cycle Progression (2007, background): “We measured expression profiles at 24 h, when mRNA silencing is maximal but secondary transcriptional effects due to protein depletion are minimal (28).”
RNA silencing: Methods and protocols (2006, background): “In order to target one sequence specifically, you should therefore choose a fragment of about 500 bp that is within the predicted mRNA and has less than 85% identity with other genes (33).”
Finding function in novel targets: C. elegans as a model organism (2006, background): “Indeed, although RNAi has been assumed to cause a sequence specific knockdown, it has more recently become obvious that RNAi, at least in vitro , can also induce off-target effect”
Molecular mechanisms and potential therapeutical targets in Huntington's disease. (2010, background): “Finally, recent studies have highlighted the potential side effects of siRNAs, such as changes in expression of off-target genes (140, 278, 508), induction of cellular immunoreactive responses (532), or competition of exogenous RNA interference with endogenous, intracellular mRNA silencing systems (”
Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy (2005, background): “It is clear from published data that 'off-target' effects can occur in certain cell lines using 21-mer siRNA”
Large-scale production of dsRNA and siRNA pools for RNA interference utilizing bacteriophage ϕ6 RNA-dependent RNA polymerase (2007, background): “Lowering siRNA concentrations has been shown to decrease off-targeting significantly (Jackson et al. 2003; Semizarov et al. 2003).”
Highly Specific Gene Silencing by Artificial MicroRNAs in Arabidopsis[W][OA] (2006, methodology): “…so-called seed region between siRNA or miRNA positions 2 and 8 is often sufficient for target recognition in animals and can also result in reduced RNA levels, although these effects are mostly not due to cleavage guided by the small RNA (Jackson et al., 2003; Bagga et al., 2005; Lim et al., 2005).”
Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors (2005, background): “Although some questions remain about specificity and activation of off-target effect”