ArticleMolecular therapy. Nucleic acids2018
Membrane Destabilization Induced by Lipid Species Increases Activity of Phosphorothioate-Antisense Oligonucleotides.
Article in Molecular therapy. Nucleic acids, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 18 citations in OpenAlex.
- Antibody-oligonucleotide conjugates: an emerging modality for precision RNA therapeutics.Antibody therapeutics · 2026Review
- The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026Review
- The efficacy of oligonucleotide-based gene therapeutics in gene silencing.Theranostics · 2026Review
- A genome-wide CRISPR screen unveils the endosomal maturation protein WDR91 as a promoter of productive ASO activity in melanoma.Molecular therapy. Nucleic acids · 2025Article
- Quantifying the activity profile of ASO and siRNA conjugates in glioblastoma xenograft tumors in vivo.Nucleic acids research · 2024Article
- A novel aptamer-based small RNA delivery platform and its application to cancer therapy.Genes & diseases · 2023Article
- Enhancing the Effectiveness of Oligonucleotide Therapeutics Using Cell-Penetrating Peptide Conjugation, Chemical Modification, and Carrier-Based Delivery Strategies.Pharmaceutics · 2023Review
- Delivery of Oligonucleotide Therapeutics: Chemical Modifications, Lipid Nanoparticles, and Extracellular Vesicles.ACS nano · 2021Review
- Development of antisense-mediated myostatin knockdown for the treatment of insulin resistance.Scientific reports · 2021Article
- High-resolution visualization and quantification of nucleic acid-based therapeutics in cells and tissues using Nanoscale secondary ion mass spectrometry (NanoSIMS).Nucleic acids research · 2021Article
- Cellular Targeting of Oligonucleotides by Conjugation with Small Molecules.Molecules (Basel, Switzerland) · 2020Review
- Phosphorothioate modified oligonucleotide-protein interactions.Nucleic acids research · 2020Article
- Antisense technology: A review.The Journal of biological chemistryReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemically modified antisense oligonucleotides with phosphorothioate linkages (PS-ASOs) mediate site-specific cleavage of RNA by RNase H1 and are broadly used as research and therapeutic tools. PS-ASOs can enter cells via endocytic pathways and escape from membrane-enclosed endocytic organelles to reach target RNAs. We recently found that lysobisphosphatidic acid is required for release of PS-ASOs from late endosomes. Here, we evaluated the effects of other lipids on PS-ASO intracellular trafficking and activities. We show that free fatty acids, ceramide, and cholesterol increase PS-ASO activities. Free fatty acids induced formation of lipid droplets without changing the intracellular localization of PS-ASOs in early or late endosomes. Ceramide and cholesterol did not obviously induce the formation of lipid droplets, but cholesterol caused enlargement of endosome size and volume. Although none of those lipids appeared to influence PS-ASO internalization or intracellular trafficking processes, all led to an increase in leakiness of late endosomes. Thus, the membrane destabilization induced by these lipids likely contributes to PS-ASO release from late endosomes, which, in turn, increases PS-ASO activity.
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.