ArticleHuman gene therapy2012
Asymmetric siRNA: new strategy to improve specificity and reduce off-target gene expression.
Article in Human gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed.
- Small Nucleic Acid Therapeutics for Ocular Diseases: Progress, Challenges, and Future Perspectives.Pharmaceutics · 2026Review
- Design, Screening and Development of Asymmetric siRNAs Targeting theBiomolecules & therapeutics · 2025Article
- Chemical Strategies to Enhance Antisense Strand Selection and Minimize Off-Target Effect-Mediated by siRNAs.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Chemistry, structure and function of approved oligonucleotide therapeutics.Nucleic acids research · 2023Review
- Delivering the Promise of Gene Therapy with Nanomedicines in Treating Central Nervous System Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Specificity of oligonucleotide gene therapy (OGT) agents.Theranostics · 2022Review
- Chemical strategies for strand selection in short-interfering RNAs.RSC advances · 2021Review
- Circular siRNAs for Reducing Off-Target Effects and Enhancing Long-Term Gene Silencing in Cells and Mice.Molecular therapy. Nucleic acids · 2018Article
- Combined shRNA over CRISPR/cas9 as a methodology to detect off-target effects and a potential compensatory mechanism.Scientific reports · 2018Article
- Strategic applications of gene expression: from drug discovery/development to bedside.The AAPS journal · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small interfering RNAs (siRNAs) have been used extensively in reverse genetic research, and many have made their way into clinical trials. The most widely used siRNA structure consists of double-stranded RNA with 19 base pairs and 2-nucleotide overhangs at the 3'-end of both strands (19+2). Although widely used, this symmetric structure bears inherent disadvantages in both research and clinical applications. One of the most common caveats is the off-target effect leading to adverse effects in clinical application. In the current study, using C-C chemokine receptor (CCR5) as a target, we have shown that 19+2 siRNA could still cause considerable global off-target effects regardless of rational design based on its thermodynamic asymmetry. However, we demonstrated that structurally asymmetric siRNA targeting CCR5 could be adopted to improve the strand specificity and greatly reduce the off-target effects without significantly compromising its on-target effects. Data from microarray analysis suggest that an unidentified mechanism resulting in global gene down-regulation might be avoided through strand shortening. Taken together, our work suggested a promising and simple way to improve strand specificity and overcome the off-target gene-expression effects without introducing more complications while retaining the efficacy of siRNA.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.