ArticleMolecular therapy. Nucleic acids2022
RNA modifications can affect RNase H1-mediated PS-ASO activity.
Article in Molecular therapy. Nucleic acids, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 21 citations in OpenAlex.
- Targeting SUV39H2 exon skipping reverses resistance to CDK4/6 inhibitors via transcriptional activation of p21.Science advances · 2026Article
- Exploring the Potential of PhosphoramideACS omega · 2026Article
- Silencing with precision: In silico strategies for antisense oligonucleotide engineering.Molecular biology reports · 2026Review
- The versatile roles of long non-coding RNAs in kidney disease.Nature reviews. Nephrology · 2026Review
- The lncRNA PHAROH augments MYC mRNA levels in insulin-producing cells by counteracting TIA1-induced MYC silencing.Scientific reports · 2026Article
- Chemical Modification Strategies for Therapeutic Oligonucleotides: Mechanism Compatibility, Design Trade-Offs, and Translational Barriers.Molecules (Basel, Switzerland) · 2026Review
- Beyond Coding Variants: RNA-Level Mechanisms in Human Disease and Precision Therapeutics.Genes · 2026Review
- Single-base 2'OMe-modified LNA and MOE gapmers selectively silenceMolecular therapy. Nucleic acids · 2026Article
- RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Review
- Synthetic short RNA in cancer.Frontiers in oncology · 2026Review
- Review
- All the sites we cannot see: Sources and mitigation of false negatives in RNA modification studies.Nature reviews. Molecular cell biology · 2025Review
- Evolution of antisense oligonucleotides: navigating nucleic acid chemistry and delivery challenges.Expert opinion on drug discovery · 2025Review
- Loss of CHOP Prevents Joint Degeneration and Pain in a Mouse Model of Pseudoachondroplasia.International journal of molecular sciences · 2024Article
- Review
- Targeting and engineering long non-coding RNAs for cancer therapy.Nature reviews. Genetics · 2024Review
- Targeting RNA with synthetic oligonucleotides: Clinical success invites new challenges.Cell chemical biology · 2024Review
- Current concepts of the crosstalk between lncRNA and E2F1: shedding light on the cancer therapy.Frontiers in pharmacology · 2024Review
- Stimuli-Responsive Nanotechnology for RNA Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Nucleic Acid-Based Approaches to Tackle KRAS Mutant Cancers.International journal of molecular sciences · 2023Review
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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
Phosphorothioate modified antisense oligonucleotides (PS-ASOs) can reduce gene expression through hybridization to target RNAs and subsequent cleavage by RNase H1. Target reduction through this mechanism is influenced by numerous features of the RNA, which modulate PS-ASO binding affinities to the RNA target, and how the PS-ASO-RNA hybrid is recognized by RNase H1 for RNA cleavage. Endogenous RNAs are frequently chemically modified, which can regulate intra- and intermolecular interactions of the RNA. The effects of PS-ASO modifications on antisense activity have been well studied; however, much less is known regarding the effects of RNA modifications on PS-ASO hybridization and RNase H1 cleavage activity. Here, we determine the effects of three different RNA modifications on PS-ASO binding and antisense activity in recombinant and cell-based systems. Some RNA modifications can reduce PS-ASO hybridization, the cleavage activity of RNase H1, or both, while other modifications had minimal effects on PS-ASO function. In addition to these direct effects, RNA modifications can also change the RNA structure, which may affect PS-ASO accessibility in a cellular context. Our results elucidate the effects of three prevalent RNA modifications on PS-ASO-mediated RNase H1 cleavage activity, and such findings will help improve PS-ASO target site selection.
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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.