ArticleThe Journal of clinical investigation1995
Binding, uptake, and intracellular trafficking of phosphorothioate-modified oligodeoxynucleotides.
Article in The Journal of clinical investigation, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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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.
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Who cites it
70 citing papers in PubMed, 314 citations in OpenAlex.
- The efficacy of oligonucleotide-based gene therapeutics in gene silencing.Theranostics · 2026Review
- Molecular treatment options for patients carryingMolecular therapy. Nucleic acids · 2025Article
- Peptide Conjugates of a 2'-ACS omega · 2023Article
- GOLGA8 increases bulk antisense oligonucleotide uptake and activity in mammalian cells.Molecular therapy. Nucleic acids · 2023Article
- Future directions for medicinal chemistry in the field of oligonucleotide therapeutics.RNA (New York, N.Y.) · 2023Article
- The Influence of Proteins on Fate and Biological Role of Circulating DNA.International journal of molecular sciences · 2022Review
- Quantitative Measurement of Cytosolic and Nuclear Penetration of Oligonucleotide Therapeutics.ACS chemical biology · 2022Article
- Gene Regulation Using Nanodiscs Modified with HIF-1-α Antisense Oligonucleotides.Bioconjugate chemistry · 2022Article
- Antisense oligonucleotide activity in tumour cells is influenced by intracellular LBPA distribution and extracellular vesicle recycling.Communications biology · 2021Article
- A critical analysis of methods used to investigate the cellular uptake and subcellular localization of RNA therapeutics.Nucleic acids research · 2020Review
- Systemic Evaluation of Chimeric LNA/2'-O-Methyl Steric Blockers for Myotonic Dystrophy Type 1 Therapy.Nucleic acid therapeutics · 2020Article
- Pharmacokinetic Studies of Antisense Oligonucleotides Using MALDI-TOF Mass Spectrometry.Frontiers in pharmacology · 2020Article
- Combining Engineered U1 snRNA and Antisense Oligonucleotides to Improve the Treatment of a BBS1 Splice Site Mutation.Molecular therapy. Nucleic acids · 2019Article
- A novel and translational role for autophagy in antisense oligonucleotide trafficking and activity.Nucleic acids research · 2019Article
- Advances in the Understanding of Skin Cancer: Ultraviolet Radiation, Mutations, and Antisense Oligonucleotides as Anticancer Drugs.Molecules (Basel, Switzerland) · 2019Review
- Selective tissue targeting of synthetic nucleic acid drugs.The Journal of clinical investigation · 2019Review
- Quantitative fluorescence imaging determines the absolute number of locked nucleic acid oligonucleotides needed for suppression of target gene expression.Nucleic acids research · 2019Article
- COPII vesicles can affect the activity of antisense oligonucleotides by facilitating the release of oligonucleotides from endocytic pathways.Nucleic acids research · 2018Article
- PEGylation of therapeutic oligonucletides: From linear to highly branched PEG architectures.Nano research · 2018Article
- Receptor-Mediated Uptake of Phosphorothioate Antisense Oligonucleotides in Different Cell Types of the Liver.Nucleic acid therapeutics · 2018Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
An enhanced appreciation of uptake mechanisms and intracellular trafficking of phosphorothioate modified oligodeoxynucleotides (P-ODN) might facilitate the use of these compounds for experimental and therapeutic purposes. We addressed these issues by identifying cell surface proteins with which P-ODN specifically interact, studying P-ODN internalization mechanisms, and by tracking internalized P-ODN through the cell using immunochemical and ultrastructural techniques. Chemical cross-linking studies with a biotin-labeled P-ODN (bP-ODN), revealed the existence of five major cell surface P-ODN binding protein groups ranging in size from approximately 20-143 kD. Binding to these proteins was competitively inhibited with unlabeled P-ODN, but not free biotin, suggesting specificity of the interactions. Additional experiments suggested that binding proteins likely exist as single chain structures, and that carbohydrate moieties may play a role in P-ODN binding. Uptake studies with 35S-labeled P-ODN revealed that endocytosis, mediated by a receptor-like mechanism, predominated at P-ODN concentrations < 1 microM, whereas fluid-phase endocytosis prevailed at higher concentrations. Cell fractionation and ultrastructural analysis demonstrated the presence of ODN in clathrin coated pits, and in vesicular structures consistent with endosomes and lysosomes. Labeled ODN were also found in significant amounts in the nucleus, while none was associated with ribosomes, or ribosomes associated with rough endoplasmic reticulum (ER). Since nuclear uptake was not blocked by wheat germ agglutinin or concanavalin A, a nucleoporin independent, perhaps diffusion driven, import process is suggested. These data imply that antisense DNA may exert their effect in the nucleus. They also suggest rational ways to design ODN which might increase their efficiency.
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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.