ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
Modified siRNA structure with a single nucleotide bulge overcomes conventional siRNA-mediated off-target silencing.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 43 citations in OpenAlex.
- Construction and Characterization of Paired Patient-Derived Cell Models for Solitary Fibrous Tumors (SFTs).Cancers · 2026Article
- Engineering miRNA features into siRNAs: Guide-strand bulges are compatible with gene repression.Molecular therapy. Nucleic acids · 2022Article
- Specificity of oligonucleotide gene therapy (OGT) agents.Theranostics · 2022Review
- Chemical strategies for strand selection in short-interfering RNAs.RSC advances · 2021Review
- Effective tools for RNA-derived therapeutics: siRNA interference or miRNA mimicry.Theranostics · 2021Review
- Systematic Screening, Rational Development, and Initial Optimization of Efficacious RNA Silencing Agents for Human Rod Opsin Therapeutics.Translational vision science & technology · 2019Article
- The double edge of anti-CD40 siRNA therapy: It increases renal microcapillar density but favours the generation of an inflammatory milieu in the kidneys of ApoEJournal of inflammation (London, England) · 2019Article
- Exploring PAZ/3'-overhang interaction to improve siRNA specificity. A combined experimental and modeling study.Chemical science · 2018Article
- Controlling miRNA-like off-target effects of an siRNA with nucleobase modifications.Organic & biomolecular chemistry · 2017Article
- Abasic pivot substitution harnesses target specificity of RNA interference.Nature communications · 2015Article
- Synthetic RNAs for Gene Regulation: Design Principles and Computational Tools.Frontiers in bioengineering and biotechnology · 2014Review
- Design of siRNA Therapeutics from the Molecular Scale.Pharmaceuticals (Basel, Switzerland) · 2013Article
- An evaluation of oligonucleotide-based therapeutic strategies for polyQ diseases.BMC molecular biology · 2012Article
- Development of Therapeutic-Grade Small Interfering RNAs by Chemical Engineering.Frontiers in genetics · 2012Article
- Prospect of induced pluripotent stem cell genetic repair to cure genetic diseases.Stem cells international · 2012Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Off-target gene silencing is a major concern when using RNA interference. Imperfect pairing of the antisense strand with unintended mRNA targets is one of the main causes of small interfering RNA (siRNA) off-target silencing. To overcome this, we have developed "bulge-siRNA," a modified siRNA backbone structure with a single nucleotide (nt) bulge placed in the antisense strand. We found that siRNAs with a bulge at position 2 of the antisense strand were able to discriminate better between perfectly matched and mismatched targets, with no loss in silencing of the intended target. Genome-wide analysis also revealed that the bulge-siRNAs significantly reduced off-target silencing of transcripts with complementarity to the seed region of the siRNA antisense strand. When compared to 2'-methoxy ribosyl (2'-OMe) modified siRNAs previously developed to alleviate antisense off-target silencing; the bulge modification could better discriminate between on- versus off-targets. Our results suggest that the bulge-siRNA structure is a simple, yet superior alternative to chemical modifications for minimizing off-target silencing triggered by conventional siRNA structures.
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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.