ArticleNucleic acids research2018
COPII vesicles can affect the activity of antisense oligonucleotides by facilitating the release of oligonucleotides from endocytic pathways.
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 32 papers.
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Who cites it
32 citing papers in PubMed, 41 citations in OpenAlex.
- Chemical Modification Strategies for Therapeutic Oligonucleotides: Mechanism Compatibility, Design Trade-Offs, and Translational Barriers.Molecules (Basel, Switzerland) · 2026Review
- The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026Review
- Naked antisense oligonucleotides remain endolysosomally sequestered despite induced membrane damage.bioRxiv : the preprint server for biology · 2026Article
- Phosphorothioate antisense oligonucleotide induced innate immune activation is attenuated by tryptophan oxidation products.Nucleic acids research · 2026Article
- Heteroduplex oligonucleotide technology boosts gene knockdown in cardiac and skeletal muscles.Nucleic acids research · 2026Article
- Ligand Valency and Linker Design Dictate the Efficacy of CI-M6PR-Mediated Targeted Delivery of M6P-siRNA Conjugates.ACS omega · 2025Article
- An unbiased whole-genome open reading frame overexpression screen identifies B3GALT2, a novel inducer of cellular ASO activity.Molecular therapy. Nucleic acids · 2025Article
- A CRISPR/Cas9 screen reveals proteins at the endosome-Golgi interface that modulate cellular anti-sense oligonucleotide activity.Nature communications · 2025Article
- Endosomal Escape and Nuclear Localization: Critical Barriers for Therapeutic Nucleic Acids.Molecules (Basel, Switzerland) · 2024Review
- The bench to bedside journey of tricyclo-DNA antisense oligonucleotides for the treatment of Duchenne muscular dystrophy.RSC medicinal chemistry · 2024Review
- Recent advances in methods for quantifying the cell penetration of macromolecules.Current opinion in chemical biology · 2024Review
- The Coming Age of Antisense Oligos for the Treatment of Hepatic Ischemia/Reperfusion (IRI) and Other Liver Disorders: Role of Oxidative Stress and Potential Antioxidant Effect.Antioxidants (Basel, Switzerland) · 2024Review
- Between hope and reality: treatment of genetic diseases through nucleic acid-based drugs.Communications biology · 2024Review
- Chloroquine and cytosolic galectins affect endosomal escape of antisense oligonucleotides after Stabilin-mediated endocytosis.Molecular therapy. Nucleic acids · 2023Article
- Drug Discovery Perspectives of Antisense Oligonucleotides.Biomolecules & therapeutics · 2023Review
- Article
- Insights into innate immune activation via PS-ASO-protein-TLR9 interactions.Nucleic acids research · 2022Article
- New approaches to moderate CRISPR-Cas9 activity: Addressing issues of cellular uptake and endosomal escape.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Perinuclear positioning of endosomes can affect PS-ASO activities.Nucleic acids research · 2021Article
- Safety Testing of an Antisense Oligonucleotide Intended for Pediatric Indications in the Juvenile Göttingen Minipig, including an Evaluation of the Ontogeny of Key Nucleases.Pharmaceutics · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNase H1-dependent, phosphorothioate-modified antisense oligonucleotides (PS-ASOs) can enter cells through endocytic pathways and need to be released from the membrane-enclosed organelles, a limiting step for antisense activity. Accumulating evidence has suggested that productive PS-ASO release mainly occurs from late endosomes (LEs). However, how PS-ASOs escape from LEs is not well understood. Here, we report that upon PS-ASO incubation, COPII vesicles, normally involved in ER-Golgi transport, can re-locate to PS-ASO-containing LEs. Reduction of COPII coat proteins significantly decreased PS-ASO activity, without affecting the levels of PS-ASO uptake and early-to-late endosome transport, but caused slower PS-ASO release from LEs. COPII co-localization with PS-ASOs at LEs does not require de novo assembly of COPII at ER. Interestingly, reduction of STX5 and P115, proteins involved in tethering and fusion of COPII vesicles with Golgi membranes, impaired COPII re-localization to LEs and decreased PS-ASO activity. STX5 can re-locate to LEs upon PS-ASO incubation, can bind PS-ASOs, and the binding appears to be required for this pathway. Our study reveals a novel release pathway in which PS-ASO incubation causes LE re-localization of STX5, which mediates the recruitment of COPII vesicles to LEs to facilitate endosomal PS-ASO release, and identifies another key PS-ASO binding protein.
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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.