ArticleCommunications biology2021
Antisense oligonucleotide activity in tumour cells is influenced by intracellular LBPA distribution and extracellular vesicle recycling.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- EPHA2/CD44-directed trafficking enhances endosomal leakiness and antisense therapy delivery.The Journal of cell biology · 2026Article
- Neural Stem Cell-Derived Extracellular Vesicles Improve CNS Delivery and Therapeutic Efficacy of Antisense Oligonucleotide in Amyotrophic Lateral Sclerosis.Journal of extracellular vesicles · 2026Article
- Antibody-oligonucleotide conjugates: an emerging modality for precision RNA therapeutics.Antibody therapeutics · 2026Review
- Naked antisense oligonucleotides remain endolysosomally sequestered despite induced membrane damage.bioRxiv : the preprint server for biology · 2026Article
- Microglia-specific regulation of lipid metabolism in Alzheimer's disease revealed by microglial depletion in 5xFAD Mice.Nature communications · 2025Article
- Article
- 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
- Matrix-associated extracellular vesicles modulate smooth muscle cell adhesion and directionality by presenting collagen VI.bioRxiv : the preprint server for biology · 2025Article
- Article
- Targeting the splicing factor SNRPB inhibits endometrial cancer progression by retaining the POLD1 intron.Experimental & molecular medicine · 2025Article
- Review
- ASP210: a potent oligonucleotide-based inhibitor effective against TKI-resistant CML cells.American journal of physiology. Cell physiology · 2024Article
- Lysosomal phospholipase A2 contributes to the biosynthesis of the atypical late endosome lipid bis(monoacylglycero)phosphate.Communications biology · 2023Article
- Effective Reduction of SARS-CoV-2 RNA Levels Using a Tailor-Made Oligonucleotide-Based RNA Inhibitor.Viruses · 2022Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Next generation modified antisense oligonucleotides (ASOs) are commercially approved new therapeutic modalities, yet poor productive uptake and endosomal entrapment in tumour cells limit their broad application. Here we compare intracellular traffic of anti KRAS antisense oligonucleotide (AZD4785) in tumour cell lines PC9 and LK2, with good and poor productive uptake, respectively. We find that the majority of AZD4785 is rapidly delivered to CD63+late endosomes (LE) in both cell lines. Importantly, lysobisphosphatidic acid (LBPA) that triggers ASO LE escape is presented in CD63+LE in PC9 but not in LK2 cells. Moreover, both cell lines recycle AZD4785 in extracellular vesicles (EVs); however, AZD4785 quantification by advanced mass spectrometry and proteomic analysis reveals that LK2 recycles more AZD4785 and RNA-binding proteins. Finally, stimulating LBPA intracellular production or blocking EV recycling enhances AZD4785 activity in LK2 but not in PC9 cells thus offering a possible strategy to enhance ASO potency in tumour cells with poor productive uptake of ASOs.
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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.