ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
Uptake, efficacy, and systemic distribution of naked, inhaled short interfering RNA (siRNA) and locked nucleic acid (LNA) antisense.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed.
- RNA-Loaded Nanoparticles for Targeted Lung Delivery.Biomedicines · 2026Review
- Restoring chloride efflux in cystic fibrosis with TMEM16a antisense oligonucleotides.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Tissue pharmacokinetics of antisense oligonucleotides.Molecular therapy. Nucleic acids · 2024Article
- Aerosol pulmonary immune engineering.Advanced drug delivery reviews · 2023Review
- Intratracheally administered LNA gapmer antisense oligonucleotides induce robust gene silencing in mouse lung fibroblasts.Nucleic acids research · 2022Article
- An intranasal ASO therapeutic targeting SARS-CoV-2.Nature communications · 2022Article
- Antisense oligonucleotides targeting ORF1b block replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Frontiers in microbiology · 2022Article
- Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality?Frontiers in immunology · 2022Review
- Synthesis and Characterization of Click Nucleic Acid Conjugated Polymeric Microparticles for DNA Delivery Applications.Biomacromolecules · 2021Article
- Inhibition of SARS-CoV-2 by Targeting Conserved Viral RNA Structures and Sequences.Frontiers in chemistry · 2021Review
- Considerations for setting occupational exposure limits for novel pharmaceutical modalities.Regulatory toxicology and pharmacology : RTP · 2020Review
- Comprehensive analysis of drugs to treat SARS‑CoV‑2 infection: Mechanistic insights into current COVID‑19 therapies (Review).International journal of molecular medicine · 2020Review
- Combined Chemisorption and Complexation Generate siRNA Nanocarriers with Biophysics Optimized for Efficient Gene Knockdown and Air-Blood Barrier Crossing.ACS applied materials & interfaces · 2020Article
- Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS.EMBO reports · 2020Article
- Nuclear and Cytoplasmatic Quantification of Unconjugated, Label-Free Locked Nucleic Acid Oligonucleotides.Nucleic acid therapeutics · 2020Article
- Aberrant MicroRNAomics in Pulmonary Complications: Implications in Lung Health and Diseases.Molecular therapy. Nucleic acids · 2019Review
- Intratracheal Administration of siRNA Triggers mRNA Silencing in the Lung to Modulate T Cell Immune Response and Lung Inflammation.Molecular therapy. Nucleic acids · 2019Article
- The potential of antisense oligonucleotide therapies for inherited childhood lung diseases.Molecular and cellular pediatrics · 2018Review
- RIG-I-Like Receptors as Novel Targets for Pan-Antivirals and Vaccine Adjuvants Against Emerging and Re-Emerging Viral Infections.Frontiers in immunology · 2018Review
- Oligonucleotide Therapies for the Lung: Ready to Return to the Clinic?Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) promise specific correction of disease-causing gene expression. Therapeutic implementation, however, has been forestalled by poor delivery to the appropriate tissue, cell type, and subcellular compartment. Topical administration is considered to circumvent these issues. The availability of inhalation devices and unmet medical need in lung disease has focused efforts in this tissue. We report the development of a novel cell sorting method for quantitative, cell type-specific analysis of siRNA, and locked nucleic acid (LNA) ASO uptake and efficacy after intratracheal (i.t.) administration in mice. Through fluorescent dye labeling, we compare the utility of this approach to whole animal and whole tissue analysis, and examine the extent of tissue distribution. We detail rapid systemic access and renal clearance for both therapeutic classes and lack of efficacy at the protein level in lung macrophages, epithelia, or other cell types. We nevertheless observe efficient redirection of i.t. administered phosphorothioate (PS) LNA ASO to the liver and kidney leading to targeted gene knockdown. These data suggest delivery remains a key obstacle to topically administered, naked oligonucleotide efficacy in the lung and introduce inhalation as a potentially viable alternative to injection for antisense administration to the liver and kidneys.
Indexed as
Identifiers
What OpenQuestion holds
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.