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Off-target mRNAs with partial complementarity to CD3E shRNA guide strand (CD3E shRNA off-targets)

Target
CD3E shRNA off-targets
Molecular classification
Messenger RNA, Nucleic acid
01

Overview

Off-target mRNAs with partial complementarity to CD3E shRNA guide strand refers to a class of unintended transcripts affected during RNA interference (RNAi) experiments or therapies targeting the CD3 epsilon (CD3E) gene. This phenomenon occurs when the shRNA guide strand, intended for CD3E, binds to non-target mRNAs via partial sequence homology, typically involving the 'seed' region (nucleotides 2-8) (Jackson et al., 2003). These interactions lead to the degradation or translational inhibition of the off-target mRNAs through the RNA-induced silencing complex (RISC), potentially causing cellular toxicity or confounding experimental results (Birmingham et al., 2006). In the context of CD3E, which is critical for T-cell receptor signaling and T-cell activation, off-target effects could inadvertently alter immune responses or cell viability (Sigoillot & King, 2011). Identifying these off-targets is essential for ensuring the specificity of shRNA-based tools and the safety of nucleic acid therapeutics. Researchers often use bioinformatics tools and transcriptome-wide expression profiling to predict and monitor these unintended interactions.

Other names
RNAi off-target effectsSeed-mediated off-targetsshRNA-induced off-target silencingUnintended mRNA transcriptsCD3E shRNA-mediated off-target genes
02

Mechanism of action

Sequence-specific downregulation of unintended mRNA transcripts via the RNA-induced silencing complex (RISC) due to partial sequence complementarity, primarily in the seed region (nucleotides 2-8) of the shRNA guide strand (Jackson et al., 2003; Birmingham et al., 2006).

03

Biological functions

Gene expression regulationProtein synthesis
04

Disease associations

ToxicityExperimental artifact
05

Safety considerations

Unintended gene silencingCytotoxicityFalse-positive experimental resultsSaturation of RISC machineryPhenotypic changes unrelated to CD3E knockdown
06

Interacting drugs

CD3E-targeting shRNA

1 more in the full profile.

07

Biomarkers

RNA-seq transcriptome profilingReporter gene assays for off-target activityDifferential gene expression analysis

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