ArticleNucleic acids research2013
RNA duplexes with abasic substitutions are potent and allele-selective inhibitors of huntingtin and ataxin-3 expression.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- An acyclic nucleic acid-modified siRNA targeting CAG expansions for polyglutamine disease treatment.Molecular therapy. Nucleic acids · 2026Article
- Design, validation, and functional impact of oligonucleotides for multigene silencing in Alzheimer's disease.Molecular therapy. Nucleic acids · 2026Article
- RNA chemistry and therapeutics.Nature reviews. Drug discovery · 2025Review
- Enhancing the Effectiveness of Oligonucleotide Therapeutics Using Cell-Penetrating Peptide Conjugation, Chemical Modification, and Carrier-Based Delivery Strategies.Pharmaceutics · 2023Review
- Emerging Therapies for Huntington's Disease - Focus on N-Terminal Huntingtin and Huntingtin Exon 1.Biologics : targets & therapy · 2022Review
- Thermostability, Tunability, and Tenacity of RNA as Rubbery Anionic Polymeric Materials in Nanotechnology and Nanomedicine-Specific Cancer Targeting with Undetectable Toxicity.Chemical reviews · 2021Review
- Selective suppression of polyglutamine-expanded protein by lipid nanoparticle-delivered siRNA targeting CAG expansions in the mouse CNS.Molecular therapy. Nucleic acids · 2021Article
- Artificial miRNAs targeting CAG repeat expansion in ORFs cause rapid deadenylation and translation inhibition of mutant transcripts.Cellular and molecular life sciences : CMLS · 2021Article
- Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3.Science translational medicine · 2020Article
- Advances in oligonucleotide drug delivery.Nature reviews. Drug discovery · 2020Review
- Recent advances in molecular therapies for neurological disease: triplet repeat disorders.Human molecular genetics · 2019Review
- Exploring PAZ/3'-overhang interaction to improve siRNA specificity. A combined experimental and modeling study.Chemical science · 2018Article
- Reduction of Huntington's Disease RNA Foci by CAG Repeat-Targeting Reagents.Frontiers in cellular neuroscience · 2017Article
- Article
- Abasic pivot substitution harnesses target specificity of RNA interference.Nature communications · 2015Article
- Oligonucleotide Therapies: The Past and the Present.Human gene therapy · 2015Review
- Effect of 2'-O-methyl/thiophosphonoacetate-modified antisense oligonucleotides on huntingtin expression in patient-derived cells.Artificial DNA, PNA & XNA · 2014Article
- In vivo evaluation of candidate allele-specific mutant huntingtin gene silencing antisense oligonucleotides.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Allele-selective inhibition of mutant atrophin-1 expression by duplex and single-stranded RNAs.Biochemistry · 2014Article
- Oligonucleotide-based strategies to combat polyglutamine diseases.Nucleic acids research · 2014Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Abasic substitutions within DNA or RNA are tools for evaluating the impact of absent nucleobases. Because of the importance of abasic sites in genetic damage, most research has involved DNA. Little information is available on the impact of abasic substitutions within RNA or on RNA interference (RNAi). Here, we examine the effect of abasic substitutions on RNAi and allele-selective gene silencing. Huntington's disease (HD) and Machado Joseph Disease (MJD) are severe neurological disorders that currently have no cure. HD and MJD are caused by an expansion of CAG repeats within one mRNA allele encoding huntingtin (HTT) and ataxin-3 (ATX-3) proteins. Agents that silence mutant HTT or ATX-3 expression would remove the cause of HD or MJD and provide an option for therapeutic development. We describe flexible syntheses for abasic substitutions and show that abasic RNA duplexes allele-selectively inhibit both mutant HTT and mutant ATX-3. Inhibition involves the RNAi protein argonaute 2, even though the abasic substitution disrupts the catalytic cleavage of RNA target by argonaute 2. Several different abasic duplexes achieve potent and selective inhibition, providing a broad platform for subsequent development. These findings introduce abasic substitutions as a tool for tailoring RNA duplexes for gene silencing.
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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.