ArticleNucleic acids research2004
DNA binding and antigene activity of a daunomycin-conjugated triplex-forming oligonucleotide targeting the P2 promoter of the human c-myc gene.
Article in Nucleic acids research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 57 citations in OpenAlex.
- Sequence-Specific Targeting of GC-Rich Gene Loci by Parallel Triplex-Forming Oligonucleotides Containing a Modified Nucleobase.bioRxiv : the preprint server for biology · 2026Article
- Development and functional evaluation of a psoralen-conjugated nucleoside mimic for triplex-forming oligonucleotides.Communications chemistry · 2025Article
- Recent Advancements in Development and Therapeutic Applications of Genome-Targeting Triplex-Forming Oligonucleotides and Peptide Nucleic Acids.Pharmaceutics · 2023Review
- The Anticancer Drug Daunomycin Directly Affects Gene Expression and DNA Structure.International journal of molecular sciences · 2023Article
- Triplex-forming oligonucleotides as an anti-gene technique for cancer therapy.Frontiers in pharmacology · 2022Review
- Transcriptional Reprogramming and Novel Therapeutic Approaches for Targeting Prostate Cancer Stem Cells.Frontiers in oncology · 2019Review
- Synthesis and triplex-forming properties of oligonucleotides capable of recognizing corresponding DNA duplexes containing four base pairs.Nucleic acids research · 2015Article
- In vitro antiviral activity of circular triple helix forming oligonucleotide RNA towards Feline Infectious Peritonitis virus replication.BioMed research international · 2014Article
- Sequence-specific targeting of IGF-I and IGF-IR genes by camptothecins.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2010Article
- MYC and Breast Cancer.Genes & cancer · 2010Article
- Calorimetric and spectroscopic studies of aminoglycoside binding to AT-rich DNA triple helices.Biochimie · 2010Article
- TTS mapping: integrative WEB tool for analysis of triplex formation target DNA sequences, G-quadruplets and non-protein coding regulatory DNA elements in the human genome.BMC genomics · 2009Article
- Cross-linking to an interrupted polypurine sequence with a platinum-modified triplex-forming oligonucleotide.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2009Article
- Discovery of novel triple helical DNA intercalators by an integrated virtual and actual screening platform.Nucleic acids research · 2009Article
- MYC in breast tumor progression.Expert review of anticancer therapy · 2008Review
- The triple helix: 50 years later, the outcome.Nucleic acids research · 2008Review
- Sequence-specific triple helix formation with genomic DNA.Biochemistry · 2007Article
- Bioconjugation of oligonucleotides for treating liver fibrosis.Oligonucleotides · 2007Review
- Growth inhibition and apoptosis induced by daunomycin-conjugated triplex-forming oligonucleotides targeting the c-myc gene in prostate cancer cells.Nucleic acids research · 2006Article
- Novel GC-rich DNA-binding compound produced by a genetically engineered mutant of the mithramycin producer Streptomyces argillaceus exhibits improved transcriptional repressor activity: implications for cancer therapy.Nucleic acids research · 2006Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Triplex-forming oligonucleotides (TFO) that bind DNA in a sequence-specific manner might be used as selective repressors of gene expression and gene-targeted therapeutics. However, many factors, including instability of triple helical complexes in cells, limit the efficacy of this approach. In the present study, we tested whether covalent linkage of a TFO to daunomycin, which is a potent DNA-intercalating agent and anticancer drug, could increase stability of the triple helix and activity of the oligonucleotide in cells. The 11mer daunomycin-conjugated GT (dauno-GT11) TFO targeted a sequence upstream of the P2 promoter, a site known to be critical for transcription of the c-myc gene. Band-shift assays showed that the dauno-GT11 formed triplex DNA with enhanced stability compared to the unmodified TFO. Band shift and footprinting experiments demonstrated that binding of dauno-GT11 was highly sequence-specific with exclusive binding to the 11 bp target site in the c-myc promoter. The daunomycin-conjugated TFO inhibited transcription in vitro and reduced c-myc promoter activity in prostate and breast cancer cells. The daunomycin-conjugated TFO was taken up by cells with a distinctive intracellular distribution compared to free daunomycin. However, cationic lipid-mediated delivery was required for enhanced cellular uptake, nuclear localization and biological activity of the TFO in cells. Dauno-GT11 reduced transcription of the endogenous c-myc gene in cells, but did not affect expression of non-target genes, such as ets-1 and ets-2, which contained very similar target sequences in their promoters. Daunomycin-conjugated control oligonucleotides unable to form triplex DNA with the target sequence did not have any effect in these assays, indicating that daunomycin was not directly responsible for the activity of daunomycin-conjugated TFO. Thus, attachment of daunomycin resulted in increased triplex stability and biological activity of the 11mer GT-rich TFO without compromising its specificity. These results encourage further testing of this approach to develop novel antigene therapeutics.
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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.