GEO DataSets

(Submitter supplied) In addition to silencing intended target genes, transfected siRNAs regulate numerous unintended transcripts through a mechanism in which the equivalent of a microRNA-like seed region in the siRNA recognizes complementary sequences in transcript 3' UTRs. The ability to limit such off-target effects would substantially facilitate accurate interpretation of RNA interference (RNAi) experiments and thus greatly enhance their value. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platforms:

GPL4372 GPL3991 GPL10379

29 Samples

Download data: CEL, TXT

(Submitter supplied) Transfected siRNAs and miRNAs regulate numerous transcripts that have only limited complementarity to the active strand of the RNA duplex. This process reflects natural target regulation by miRNAs, but is an unintended (“off-target”) consequence of siRNA-mediated silencing. Here we demonstrate that this unintended off-target silencing is widespread, and occurs in a manner reminiscent of target silencing by miRNAs. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platforms:

GPL2029 GPL3991 GPL3992

68 Samples

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(Submitter supplied) Transfected siRNAs regulate numerous transcripts sharing limited complementarity to the RNA duplex. This unintended (“off-target”) silencing can hinder the use of RNAi to define gene function. Here we describe position-specific, sequence-independent chemical modifications that reduced silencing of partially-complementary transcripts by all siRNAs tested. Silencing of perfectly-matched targets was unaffected by these modifications. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platforms:

GPL3991 GPL3992

61 Samples

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(Submitter supplied) This study demonstrates that siRNA off-targets (e.g. 3'UTR off-targets), can be significantly reduced when cells are treated with a relatively low dose of siRNA (e.g. 1nM) that is sufficient to effectively silence the intended target.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL9324

54 Samples

Download data: CEL

(Submitter supplied) siRNAs mediate sequence-specific gene silencing in cultured mammalian cells but also silence unintended transcripts. Many siRNA off-target transcripts match the guide-strand ‘‘seed region,’’ similar to the way microRNAs match their target sites. The extent to which this seed-matched, microRNA-like, off-target silencing affects the specificity of therapeutic siRNAs in vivo is currently unknown. Here, we compare microRNA-like off-target regulations in mouse liver in vivo with those seen in cell culture for a series of therapeutic candidate siRNAs targeting Apolipoprotein B (APOB). more...

Organism:

Homo sapiens; Mus musculus

Type:

Non-coding RNA profiling by array; Expression profiling by array

Platforms:

GPL6794 GPL6793

81 Samples

Download data: CEL

(Submitter supplied) Embryonic lung fibroblasts (HLF) infected with either control lentivirus (GSM3892), or lentivirus expressing MRG15 and MRGX small hairpin RNAs from the H1 polIII promoter (GSM3891). The MRG15 shRNA induces an interferon response that is unrelated to silencing of MRG15. Keywords: other

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS201

Platform:

GPL247

2 Samples

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Embryonic lung fibroblasts (HLF) infected with control lentivirus, or lentivirus expressing MRG15 and MRGX small hairpin RNAs from the H1 polIII promoter. The MRG15 shRNA induces an interferon response that is unrelated to silencing of MRG15.

Organism:

Homo sapiens

Type:

Expression profiling by array, log ratio, 2 cell line sets

Platform:

GPL247

Series:

GSE282

2 Samples

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(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platforms:

GPL18695 GPL16686

21 Samples

Download data: CEL

(Submitter supplied) Short interfering RNAs (siRNA) are widely used as tool for gene inactivation in basic research and therapeutic applications. One of the major shortcomings of siRNA experiments are sequence-specific Off-target effects. Such effects are largely unpredictable because siRNAs can affect partially complementary sequences and function like microRNAs (miRNAs), which inhibit gene expression on mRNA stability or translational levels. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL18695

12 Samples

Download data: CEL

(Submitter supplied) Short interfering RNAs (siRNA) are widely used as tool for gene inactivation in basic research and therapeutic applications. One of the major shortcomings of siRNA experiments are sequence-specific Off-target effects. Such effects are largely unpredictable because siRNAs can affect partially complementary sequences and function like microRNAs (miRNAs), which inhibit gene expression on mRNA stability or translational levels. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16686

9 Samples

Download data: CEL

(Submitter supplied) RNA interference (RNAi) is becoming routine in scientific discovery and treating human disease. However, its applications are hampered by unwanted effects. The RNA-Seq analyses from mouse liver samples expressing various anti-HCV shRNAs show that weak base-pairing in both seed and 3’ regions is required to achieve minimal off-targeting effect.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

20 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens; Mus musculus; synthetic construct; Gallus gallus

Type:

Expression profiling by high throughput sequencing; Non-coding RNA profiling by high throughput sequencing; Other

5 related Platforms

179 Samples

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(Submitter supplied) Two shRNAs were placed into expression vectors harboring mir30 microRNA scaffold and an optimized scaffold where the artificial restriction sights in mir30 have been removed. After infection and selection shRNA processing was assessed by small-RNA cloning. For both shRNAs, placement into the optimized scaffold resulted in a ~two-fold increase in processing (based on smallRNA levels).

Organism:

Homo sapiens; Gallus gallus

Type:

Non-coding RNA profiling by high throughput sequencing

Platforms:

GPL15520 GPL19064

8 Samples

Download data: TXT

(Submitter supplied) shRNAs selected with the shERWOOD algorithm were converted to have a U at the 5' end of their guide. When endogenous 1U shRNAs were compared to artificial shRNA via the sensor algorithm, the endogenous shRNAs were found to be more efficacious.

Organism:

synthetic construct

Type:

Other

Platform:

GPL15228

11 Samples

Download data: TXT

(Submitter supplied) Sub-genomewide shRNA libraries were constructed using the current RNAi consortium constructs as well as using the DSIR (siRNA algoirthm) and a novel shRNA specific algorithm (shERWOOD). All libraries were placed into mir30 expression vectors. The shERWOOD libraries were also placed in a vector harboring an optimized mir cassette (ultramir). Each library was screened using the pancreatic cell line A385. more...

Organism:

synthetic construct

Type:

Other

Platform:

GPL15228

24 Samples

Download data: TXT

(Submitter supplied) shRNAs were assessed for off-target effects by comparing the gene expression profiles of cells that they had been infected into. shRNAs designed with the shERWOOD algorithm and house in the ultramir microRNA scafold were found to have very little off targeting.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

40 Samples

Download data: TXT

(Submitter supplied) Purpose: Generate a large, high quality database of paired shRNA efficacy/sequence datapoints.

Organism:

synthetic construct

Type:

Other

Platform:

GPL9423

96 Samples

Download data: TXT

(Submitter supplied) We wanted to identify regions of active and open chromatin in a pre-B-cell model of Acute Lymphoblastic Leukemia (ALL). We did not stimulate or treat the cells, we merely maintained them in culture. We chose these conditions because we were building a computational model and needed a baseline read of histone activation.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

3 Samples

Download data: BED

(Submitter supplied) Preclinical mechanistic studies have pointed towards RNAi-mediated off-target effects as a major driver of hepatotoxicity for GalNAc-siRNA conjugates. Here we demonstrate that a single glycol nucleic acid (GNA) modification can substantially reduce siRNA seed-mediated binding to off-target transcripts while maintaining on-target activity. In siRNAs with established off-target effects leading to hepatotoxicity, these Enhanced Stabilization Chemistry plus (ESC+) designs exhibit a substantially improved therapeutic window in rat. more...

Organism:

Rattus norvegicus; Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL20084 GPL18573

157 Samples

Download data: TXT

(Submitter supplied) Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient, inducible, and reversible suppression of any gene upon introduction of a synthetic target sequence into non-coding transcript regions. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL30173

60 Samples

Download data: TXT