ArticleScientific reports2017
Influence of mismatched and bulged nucleotides on SNP-preferential RNase H cleavage of RNA-antisense gapmer heteroduplexes.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 18 citations in OpenAlex.
- An antisense oligonucleotide targeting STK25 as a long-acting therapeutic candidate for early MASLD.Molecular therapy. Nucleic acids · 2026Article
- ClinASO: An open-source platform for rapid drug discovery of gapmer antisense oligonucleotides.Molecular therapy. Nucleic acids · 2026Article
- Personalized allele-specific antisense oligonucleotides for GNAO1-neurodevelopmental disorder.Molecular therapy. Nucleic acids · 2025Article
- Strategies to improve the design of gapmer antisense oligonucleotide on allele-specific silencing.Molecular therapy. Nucleic acids · 2024Article
- Allele-Selective Thiomorpholino Antisense Oligonucleotides as a Therapeutic Approach for Fused-in-Sarcoma Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2024Article
- Small interfering RNA-mediated allele-selective silencing of von Willebrand factor in vitro and in vivo.Blood advances · 2023Article
- Reduction of Off-Target Effects of Gapmer Antisense Oligonucleotides by Oligonucleotide Extension.Molecular diagnosis & therapy · 2022Article
- Characterization ofNucleic acid therapeutics · 2021Article
- Hybridization-mediated off-target effects of splice-switching antisense oligonucleotides.Nucleic acids research · 2020Article
- Article
- A systematic study on the influence of thermodynamic asymmetry of 5'-ends of siRNA duplexes in relation to their silencing potency.Scientific reports · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study focused on determining design rules for gapmer-type antisense oligonucleotides (ASOs), that can differentiate cleavability of two SNP variants of RNA in the presence of ribonuclease H based on the mismatch type and position in the heteroduplex. We describe the influence of structural motifs formed by several arrangements of multiple mismatches (various types of mismatches and their position within the ASO/target RNA duplex) on RNase H cleavage selectivity of five different SNP types. The targets were mRNA fragments of APP, SCA3, SNCA and SOD1 genes, carrying C-to-G, G-to-C, G-to-A, A-to-G and C-to-U substitutions. The results show that certain arrangements of mismatches enhance discrimination between wild type and mutant SNP alleles of RNA in vitro as well as in HeLa cells. Among the over 120 gapmers tested, we found two gapmers that caused preferential degradation of the mutant allele APP 692 G and one that led to preferential cleavage of the mutant SNCA 53 A allele, both in vitro and in cells. However, several gapmers promoted selective cleavage of mRNA mutant alleles in in vitro experiments only.
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