ArticleNucleic acids research2022
Intratracheally administered LNA gapmer antisense oligonucleotides induce robust gene silencing in mouse lung fibroblasts.
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 24 papers.
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Who cites it
24 citing papers in PubMed, 27 citations in OpenAlex.
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- TRNAU1AP and PRPF39 establish integrated control over processing of most abundant human non-coding RNAs.Nature communications · 2026Article
- Long Non-Coding RNAs in Human Disease: An Overview of Biogenesis, Molecular Mechanism and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- Long Non-Coding RNA MALAT1 Regulates HMOX1 in Sickle Cell Disease-Associated Pulmonary Hypertension.Cells · 2026Article
- Synthetic nucleic acids in a post-agent biosecurity Era.Frontiers in bioengineering and biotechnology · 2026Article
- The efficacy of oligonucleotide-based gene therapeutics in gene silencing.Theranostics · 2026Review
- A State-of-the-Art Overview on (Epi)Genomics and Personalized Skin Rejuvenating Strategies.Pharmaceutics · 2025Review
- A review of recent advances in gene therapy, pharmacogenomics, and genetic polymorphisms in asthma.Molecular biology reports · 2025Review
- Potential ASO-based personalized treatment for Charcot-Marie-Tooth disease type 2S.Molecular therapy. Nucleic acids · 2025Article
- Systematic deletion of symmetricalNAR molecular medicine · 2024Article
- Advancing cancer treatments: The role of oligonucleotide-based therapies in driving progress.Molecular therapy. Nucleic acids · 2024Review
- Unveiling the intricacy of gapmer oligonucleotides through advanced tandem mass spectrometry approaches and scan accumulation for 2DMS.The Analyst · 2024Article
- Targeting and engineering long non-coding RNAs for cancer therapy.Nature reviews. Genetics · 2024Review
- Quantifying the activity profile of ASO and siRNA conjugates in glioblastoma xenograft tumors in vivo.Nucleic acids research · 2024Article
- Nucleic Acid Therapeutics: Successes, Milestones, and Upcoming Innovation.Nucleic acid therapeutics · 2024Review
- Tissue pharmacokinetics of antisense oligonucleotides.Molecular therapy. Nucleic acids · 2024Article
- ADAM33's Role in Asthma Pathogenesis: An Overview.International journal of molecular sciences · 2024Review
- Locked Nucleic Acid Oligonucleotides Facilitate RNA•LNA-RNA Triple-Helix Formation and ReduceInternational journal of molecular sciences · 2024Article
- Targeting RNA with synthetic oligonucleotides: Clinical success invites new challenges.Cell chemical biology · 2024Review
- Dendritic amphiphilic siRNA: Selective albumin binding,Molecular therapy. Nucleic acids · 2023Article
Corrections and comments
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Authors and funding
22 authors at 2 institutions in 1 country.
Funding
Abstract
The lung is a complex organ with various cell types having distinct roles. Antisense oligonucleotides (ASOs) have been studied in the lung, but it has been challenging to determine their effectiveness in each cell type due to the lack of appropriate analytical methods. We employed three distinct approaches to study silencing efficacy within different cell types. First, we used lineage markers to identify cell types in flow cytometry, and simultaneously measured ASO-induced silencing of cell-surface proteins CD47 or CD98. Second, we applied single-cell RNA sequencing (scRNA-seq) to measure silencing efficacy in distinct cell types; to the best of our knowledge, this is the first time scRNA-seq has been applied to measure the efficacy of oligonucleotide therapeutics. In both approaches, fibroblasts were the most susceptible to locally delivered ASOs, with significant silencing also in endothelial cells. Third, we confirmed that the robust silencing in fibroblasts is broadly applicable by silencing two targets expressed mainly in fibroblasts, Mfap4 and Adam33. Across independent approaches, we demonstrate that intratracheally administered LNA gapmer ASOs robustly induce gene silencing in lung fibroblasts. ASO-induced gene silencing in fibroblasts was durable, lasting 4-8 weeks after a single dose. Thus, lung fibroblasts are well aligned with ASOs as therapeutics.
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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.