ArticleNucleic acids research2018
Cellular uptake mediated by epidermal growth factor receptor facilitates the intracellular activity of phosphorothioate-modified antisense 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 47 papers.
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Who cites it
47 citing papers in PubMed, 73 citations in OpenAlex.
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- Extracellular Vesicles in Alzheimer's Disease: Mechanisms, Biomarkers, and Therapeutic Engineering.International journal of molecular sciences · 2026Review
- CTLA-4 Antisense Oligonucleotide Contributes to Enhanced Immunogenicity of an Adjuvanted RecombinantVaccines · 2026Article
- 2'-O-methylation and N6-methyladenosine enhance the oral delivery of small RNAs in mice.Molecular therapy. Nucleic acids · 2025Article
- Synthesis and Application of 4'-Molecules (Basel, Switzerland) · 2025Article
- Quantifying and mitigating motor phenotypes induced by antisense oligonucleotides in the central nervous system.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- 3D Bioprinting for Engineered Tissue Constructs and Patient-Specific Models: Current Progress and Prospects in Clinical Applications.Advanced materials (Deerfield Beach, Fla.) · 2024Review
- Comparing Cell Penetration of Biotherapeutics across Human Cell Lines.ACS chemical biology · 2024Article
- Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Self-delivering, chemically modified CRISPR RNAs for AAV co-delivery and genome editing in vivo.Nucleic acids research · 2024Article
- Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy.Frontiers in immunology · 2024Review
- Scaling approaches for the prediction of human clearance of LNA-i-mir-221: A retrospective validation.Current research in pharmacology and drug discovery · 2024Article
- Down syndrome and DYRK1A overexpression: relationships and future therapeutic directions.Frontiers in molecular neuroscience · 2024Review
- Comparative Studies of the Uptake and Internalization Pathways of Different Lipid Nano-Systems Intended for Brain Delivery.Pharmaceutics · 2023Article
- Post-transcriptional modification of mCell death & disease · 2023Article
- Enhancing the Effectiveness of Oligonucleotide Therapeutics Using Cell-Penetrating Peptide Conjugation, Chemical Modification, and Carrier-Based Delivery Strategies.Pharmaceutics · 2023Review
- EGFR-Targeted Cellular Delivery of Therapeutic Nucleic Acids Mediated by Boron Clusters.International journal of molecular sciences · 2022Article
- Cellular uptake, tissue penetration, biodistribution, and biosafety of threose nucleic acids: Assessing in vitro and in vivo delivery.Materials today. Bio · 2022Article
- NanoSIMS Imaging Reveals the Impact of Ligand-ASO Conjugate Stability on ASO Subcellular Distribution.Pharmaceutics · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemically modified antisense oligonucleotides (ASOs) with phosphorothioate (PS) linkages have been extensively studied as research and therapeutic agents. PS-ASOs can enter the cell and trigger cleavage of complementary RNA by RNase H1 even in the absence of transfection reagent. A number of cell surface proteins have been identified that bind PS-ASOs and mediate their cellular uptake; however, the mechanisms that lead to productive internalization of PS-ASOs are not well understood. Here, we characterized the interaction between PS-ASOs and epidermal growth factor receptor (EGFR). We found that PS-ASOs trafficked together with EGF and EGFR into clathrin-coated pit structures. Their co-localization was also observed at early endosomes and inside enlarged late endosomes. Reduction of EGFR decreased PS-ASO activity without affecting EGF-mediated signaling pathways and overexpression of EGFR increased PS-ASO activity in cells. Furthermore, reduction of EGFR delays PS-ASO trafficking from early to late endosomes. Thus, EGFR binds to PS-ASOs at the cell surface and mediates essential steps for active (productive) cellular uptake of PS-ASOs through its cargo-dependent trafficking processes which migrate PS-ASOs from early to late endosomes. This EGFR-mediated process can also serve as an additional model to better understand the mechanism of intracellular uptake and endosomal release of PS-ASOs.
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