ArticleNucleic acids research2015
Identification and characterization of intracellular proteins that bind oligonucleotides with phosphorothioate linkages.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed, 176 citations in OpenAlex.
- Integrated Assessment of the Clinical Performance of GalNAcNucleic acid therapeutics · 2019Trial
- Chemically stabilized long antisense oligonucleotides perturb RNA exosome function.Nucleic acids research · 2026Article
- Neutral Backbone Modifications Enhance the Pharmacokinetics and Biodistribution of Antibody-Oligonucleotide Conjugates with High Drug-to-Antibody Ratios.Journal of medicinal chemistry · 2026Article
- ESCRT-I complex enhances therapeutic efficacy of ASO drugs by regulating endosomal escape and glucose homeostasis.Molecular therapy. Nucleic acids · 2026Article
- The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026Review
- Synthesis of highly complex phosphorothioate-modified oligonucleotides on microarrays.Scientific reports · 2026Article
- Antisense Oligonucleotides: Technological Advances, Clinical Progress, and Expanding Therapeutic Frontiers.Pharmaceutics · 2026Review
- Identification and functional validation of intracellular protein partners of phosphorothioate splice-switching oligonucleotides using AP-MS.Molecular therapy. Nucleic acids · 2026Article
- Developing antisense oligomer biotics "asobiotics" as precision antibacterials: designs, strategies, and considerations for future success.FEMS microbiology reviews · 2026Review
- The efficacy of oligonucleotide-based gene therapeutics in gene silencing.Theranostics · 2026Review
- LncRNA Knockdown Using Gapmer Antisense Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Unraveling and controlling late-onset neurotoxicity of antisense oligonucleotides through strategic chemical modifications.Molecular therapy. Nucleic acids · 2025Article
- Review
- Biophysical and biological properties of splice-switching oligonucleotides and click conjugates containing LNA-phosphothiotriester linkages.Nucleic acids research · 2025Article
- Development of programmable RNA imaging with RNA-guided GFP via click chemistry.Nucleic acids research · 2025Article
- 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
- Endogenous Ribonucleases: Therapeutic Targeting of the Transcriptome Through Oligonucleotide-Triggered RNA Inactivation.Biomolecules · 2025Review
- Pharmaceutical perspectives on oligonucleotide therapeutics and delivery systems.Pharmacological reviews · 2025Review
- Chemical Modifications in Nucleic Acid Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2025Review
- The bench to bedside journey of tricyclo-DNA antisense oligonucleotides for the treatment of Duchenne muscular dystrophy.RSC medicinal chemistry · 2024Review
58 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the RNase H-dependent mechanism of inhibition of gene expression by chemically modified antisense oligonucleotides (ASOs) has been well characterized, little is known about the interactions between ASOs and intracellular proteins that may alter cellular localization and/or potency of ASOs. Here, we report the identification of 56 intracellular ASO-binding proteins using multi-step affinity selection approaches. Many of the tested proteins had no significant effect on ASO activity; however, some proteins, including La/SSB, NPM1, ANXA2, VARS and PC4, appeared to enhance ASO activities, likely through mechanisms related to subcellular distribution. VARS and ANXA2 co-localized with ASOs in endocytic organelles, and reduction in the level of VARS altered lysosome/ASO localization patterns, implying that these proteins may facilitate ASO release from the endocytic pathway. Depletion of La and NPM1 reduced nuclear ASO levels, suggesting potential roles in ASO nuclear accumulation. On the other hand, Ku70 and Ku80 proteins inhibited ASO activity, most likely by competition with RNase H1 for ASO/RNA duplex binding. Our results demonstrate that phosphorothioate-modified ASOs bind a set of cellular proteins that affect ASO activity via different mechanisms.
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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.