ArticleNucleic acids research2022
Insights into innate immune activation via PS-ASO-protein-TLR9 interactions.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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Who cites it
31 citing papers in PubMed, 32 citations in OpenAlex.
- Article
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- Recent Advancements in Drug Delivery Across the Blood-Brain Barrier in Amyotrophic Lateral Sclerosis (ALS).CNS neuroscience & therapeutics · 2026Review
- Differential metabolomic effects of progestagen-based estrus synchronisation in South African Dohne Merino ewes.Tropical animal health and production · 2026Article
- Direct targeting of C9ORF72 repeat RNA with fluorinated antisense oligonucleotides.Nucleic acids research · 2026Article
- Phosphorothioate antisense oligonucleotide induced innate immune activation is attenuated by tryptophan oxidation products.Nucleic acids research · 2026Article
- Antisense Oligonucleotides: Technological Advances, Clinical Progress, and Expanding Therapeutic Frontiers.Pharmaceutics · 2026Review
- Breathing lung-on-chip: a versatile tool for assessing respiratory toxicity across multiple therapeutic modalities.Archives of toxicology · 2026Article
- Role of LncRNA NEAT1 in Alzheimer's Disease: Pathophysiological Insights and Therapeutic Approaches.Neurotoxicity research · 2026Review
- The efficacy of oligonucleotide-based gene therapeutics in gene silencing.Theranostics · 2026Review
- Antisense oligonucleotide therapy mitigates autosomal dominant progressive hearing loss in a murine model of human DFNA2.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Cell-free DNA in extracellular vesicles: A candidate biomarker of schizophrenia.World journal of psychiatry · 2025Review
- Trends and Commonalities of Approved and Late Clinical-Phase RNA Therapeutics.Pharmaceutics · 2025Review
- Splice-modulating antisense oligonucleotides targeting a pathogenic intronic variant in adult polyglucosan body disease correct mis-splicing and restore enzyme activity in patient cells.Nucleic acids research · 2025Article
- In Vitro Structure-Activity Relationship Stability Study of Antisense Oligonucleotide Therapeutics Using Biological Matrices and Nucleases.Pharmacology research & perspectives · 2025Article
- Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.Signal transduction and targeted therapy · 2025Review
- Evolution of antisense oligonucleotides: navigating nucleic acid chemistry and delivery challenges.Expert opinion on drug discovery · 2025Review
- Engineering Considerations for Developing Next-Generation Oligonucleotide Therapeutics.Nature chemical engineering · 2024Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-CpG PS-ASOs can activate the innate immune system, leading to undesired outcomes. This response can vary-in part-as a function of 2'modifications and sequence. Here we investigated the molecular steps involved in the varied effects of PS-ASOs on the innate immune system. We found that pro-inflammatory PS-ASOs require TLR9 signaling based on the experimental systems used. However, the innate immunity of PS-ASOs does not correlate with their binding affinity with TLR9. Furthermore, the innate immune responses of pro-inflammatory PS-ASOs were reduced by coincubation with non-inflammatory PS-ASOs, suggesting that both pro-inflammatory and non-inflammatory PS-ASOs can interact with TLR9. We show that the kinetics of the PS-ASO innate immune responses can vary, which we speculate may be due to the existence of alternative PS-ASO binding sites on TLR9, leading to full, partial, or no activation of the pathway. In addition, we found that several extracellular proteins, including HMGB1, S100A8 and HRG, enhance the innate immune responses of PS-ASOs. Reduction of the binding affinity by reducing the PS content of PS-ASOs decreased innate immune responses, suggesting that PS-ASO-protein complexes may be sensed by TLR9. These findings thus provide critical information concerning how PS-ASOs can interact with and activate TLR9.
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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 Socratic graph.