ArticleNucleic acids research2015
2'-Fluoro-modified phosphorothioate oligonucleotide can cause rapid degradation of P54nrb and PSF.
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 62 papers.
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Who cites it
62 citing papers in PubMed, 103 citations in OpenAlex.
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- Systematic Profiling of ssODN Determinants Establishes Optimized LbCas12a-Mediated HDR for Precise Genome Editing inJournal of fungi (Basel, Switzerland) · 2026Article
- Chemical Modification Strategies for Therapeutic Oligonucleotides: Mechanism Compatibility, Design Trade-Offs, and Translational Barriers.Molecules (Basel, Switzerland) · 2026Review
- Single-base 2'OMe-modified LNA and MOE gapmers selectively silenceMolecular therapy. Nucleic acids · 2026Article
- Advances in antisense oligonucleotide treatment for cancer.Japanese journal of clinical oncology · 2026Review
- Stereo-random oligonucleotides enable efficient recruitment of ADAR in vitro and in vivo.Nature communications · 2025Article
- The Progress and Evolving Trends in Nucleic-Acid-Based Therapies.Biomolecules · 2025Review
- Application of antisense oligonucleotide drugs in amyotrophic lateral sclerosis and Huntington's disease.Translational neurodegeneration · 2025Review
- The Roles, Mechanisms, and Clinical Significance of Long Non-coding RNA MSC-AS1 in Cancer.Mini reviews in medicinal chemistry · 2025Review
- A review of the complex interplay between chemoresistance and lncRNAs in lung cancer.Journal of translational medicine · 2024Review
- Profiling the interactome of oligonucleotide drugs by proximity biotinylation.Nature chemical biology · 2024Article
- RNA interference in the era of nucleic acid therapeutics.Nature biotechnology · 2024Review
- Structure-activity relationship study of mesyl and busyl phosphoramidate antisense oligonucleotides for unaided and PSMA-mediated uptake into prostate cancer cells.Frontiers in chemistry · 2024Article
- A holistic analysis of the intrinsic and delivery-mediated toxicity of siRNA therapeutics.Advanced drug delivery reviews · 2023Review
- Advances in modification and delivery of nucleic acid drugs.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Review
- DNAzymes: Expanding the Potential of Nucleic Acid Therapeutics.Nucleic acid therapeutics · 2023Review
- Chemically modified aptamers for improving binding affinity to the target proteinsFrontiers in cell and developmental biology · 2023Review
- Development of 5-FU-modified tumor suppressor microRNAs as a platform for novel microRNA-based cancer therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- The Combination of Mesyl-Phosphoramidate Inter-Nucleotide Linkages and 2'-Nucleic acid therapeutics · 2022Article
2 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
Synthetic oligonucleotides are used to regulate gene expression through different mechanisms. Chemical modifications of the backbone of the nucleic acid and/or of the 2' moiety of the ribose can increase nuclease stability and/or binding affinity of oligonucleotides to target molecules. Here we report that transfection of 2'-F-modified phosphorothioate oligonucleotides into cells can reduce the levels of P54nrb and PSF proteins through proteasome-mediated degradation. Such deleterious effects of 2'-F-modified oligonucleotides were observed in different cell types from different species, and were independent of oligonucleotide sequence, positions of the 2'-F-modified nucleotides in the oligonucleotides, method of delivery or mechanism of action of the oligonucleotides. Four 2'-F-modified nucleotides were sufficient to cause the protein reduction. P54nrb and PSF belong to Drosophila behavior/human splicing (DBHS) family. The third member of the family, PSPC1, was also reduced by the 2'-F-modified oligonucleotides. Preferential association of 2'-F-modified oligonucleotides with P54nrb was observed, which is partially responsible for the protein reduction. Consistent with the role of DBHS proteins in double-strand DNA break (DSB) repair, elevated DSBs were observed in cells treated with 2'-F-modified oligonucleotides, which contributed to severe impairment in cell proliferation. These results suggest that oligonucleotides with 2'-F modifications can cause non-specific loss of cellular protein(s).
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