ArticleNucleic acids research2018
Structure-activity relationships and cellular mechanism of action of small molecules that enhance the delivery of oligonucleotides.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 36 citations in OpenAlex.
- Design and screening of novel endosomal escape compounds that enhance functional delivery of oligonucleotidesMolecular therapy. Nucleic acids · 2025Article
- Endosomal Escape and Nuclear Localization: Critical Barriers for Therapeutic Nucleic Acids.Molecules (Basel, Switzerland) · 2024Review
- Enhancing peptide and PMO delivery to mouse airway epithelia by chemical conjugation with the amphiphilic peptide S10.Molecular therapy. Nucleic acids · 2024Article
- Recent advances in methods for quantifying the cell penetration of macromolecules.Current opinion in chemical biology · 2024Review
- Quantifying the activity profile of ASO and siRNA conjugates in glioblastoma xenograft tumors in vivo.Nucleic acids research · 2024Article
- A novel transient receptor potential C3/C6 selective activator induces the cellular uptake of antisense oligonucleotides.Nucleic acids research · 2024Article
- Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking.Cells · 2023Review
- Drug Discovery Perspectives of Antisense Oligonucleotides.Biomolecules & therapeutics · 2023Review
- Endosomal escape of RNA therapeutics: How do we solve this rate-limiting problem?RNA (New York, N.Y.) · 2023Article
- Article
- Delivery of RNA Therapeutics: The Great Endosomal Escape!Nucleic acid therapeutics · 2022Review
- Oligonucleotide-based therapies for cystic fibrosis.Current opinion in pharmacology · 2022Review
- Endosomal Escape of Bioactives Deployed via Nanocarriers: Insights Into the Design of Polymeric Micelles.Pharmaceutical research · 2022Review
- Enhanced delivery of peptide-morpholino oligonucleotides with a small molecule to correct splicing defects in the lung.Nucleic acids research · 2021Article
- Chemical Manipulation of the Endosome Trafficking Machinery: Implications for Oligonucleotide Delivery.Biomedicines · 2021Review
- Delivery of oligonucleotide-based therapeutics: challenges and opportunities.EMBO molecular medicine · 2021Review
- Viral Mimicry as a Design Template for Nucleic Acid Nanocarriers.Frontiers in chemistry · 2021Review
- Cellular Targeting of Oligonucleotides by Conjugation with Small Molecules.Molecules (Basel, Switzerland) · 2020Review
- A critical analysis of methods used to investigate the cellular uptake and subcellular localization of RNA therapeutics.Nucleic acids research · 2020Review
- Phosphorothioate modified oligonucleotide-protein interactions.Nucleic acids research · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The pharmacological effects of antisense and siRNA oligonucleotides are hindered by the tendency of these molecules to become entrapped in endomembrane compartments thus failing to reach their targets in the cytosol or nucleus. We have previously used high throughput screening to identify small molecules that enhance the escape of oligonucleotides from intracellular membrane compartments and have termed such molecules OECs (oligonucleotide enhancing compounds). Here, we report on the structure-activity relationships of a family of OECs that are analogs of a hit that emerged from our original screen. These studies demonstrate key roles for the lipophilic aromatic groups, the tertiary nitrogen, and the carbamate moiety of the parent compound. We have also investigated the intracellular site of action of the OECs and have shown that activity is due to the release of oligonucleotides from intermediate endosomal compartments rather than from early endosomes or from highly acidic downstream compartments. At high concentrations of OECs toxicity occurs in a manner that is independent of caspases or of lysosomal cathepsins but instead involves increased plasma membrane permeability. Thus, in addition to describing specific characteristics of this family of OECs, the current study provides insights into basic mechanisms of oligonucleotide trafficking and their implications for oligonucleotide delivery.
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.