ArticleProceedings of the National Academy of Sciences of the United States of America2000
Unambiguous demonstration of triple-helix-directed gene modification.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 66 citations in OpenAlex.
- Triplex-forming oligonucleotides as an anti-gene technique for cancer therapy.Frontiers in pharmacology · 2022Review
- Purine- and pyrimidine-triple-helix-forming oligonucleotides recognize qualitatively different target sites at the ribosomal DNA locus.RNA (New York, N.Y.) · 2018Article
- Targeting and processing of site-specific DNA interstrand crosslinks.Environmental and molecular mutagenesis · 2010Review
- A structural analysis of the group II intron active site and implications for the spliceosome.RNA (New York, N.Y.) · 2010Article
- Asymmetric DNA requirements in Xer recombination activation by FtsK.Nucleic acids research · 2009Article
- The triple helix: 50 years later, the outcome.Nucleic acids research · 2008Review
- Sequence-specific triple helix formation with genomic DNA.Biochemistry · 2007Article
- Third strand-mediated psoralen-induced correction of the sickle cell mutation on a plasmid transfected into COS-7 cells.Gene therapy · 2007Article
- The paperclip triplex: understanding the role of apex residues in tight turns.Biophysical journal · 2006Article
- Exploring the reasons for the large density of triplex-forming oligonucleotide target sequences in the human regulatory regions.BMC genomics · 2006Article
- Antiproliferative activity of a triplex-forming oligonucleotide recognizing a Ki-ras polypurine/polypyrimidine motif correlates with protein binding.Cancer gene therapy · 2004Article
- Triplex-forming oligonucleotide target sequences in the human genome.Nucleic acids research · 2004Article
- Chromosomal site-specific double-strand breaks are efficiently targeted for repair by oligonucleotides in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- Therapeutic modulation of endogenous gene function by agents with designed DNA-sequence specificities.Nucleic acids research · 2003Review
- Branched oligonucleotides induce in vivo gene conversion of a mutated EGFP reporter.Gene therapy · 2003Article
- The potential for gene repair via triple helix formation.The Journal of clinical investigation · 2003Review
- Effect of DNA target sequence on triplex formation by oligo-2'-deoxy- and 2'-O-methylribonucleotides.Nucleic acids research · 2003Article
- Unique condensation patterns of triplex DNA: physical aspects and physiological implications.Nucleic acids research · 2002Article
- Human XPA and RPA DNA repair proteins participate in specific recognition of triplex-induced helical distortions.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- Repair of triplex-directed DNA alkylation by nucleotide excision repair.Nucleic acids research · 2001Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple-helix-forming oligonucleotides (TFOs), which can potentially modify target genes irreversibly, represent promising tools for antiviral therapies. However, their effectiveness on endogenous genes has yet to be unambiguously demonstrated. To monitor endogenous gene modification by TFOs in a yeast model, we inactivated an auxotrophic marker gene by inserting target sequences of interest into its coding region. The genetically engineered yeast cells then were treated with psoralen-linked TFOs followed by UV irradiation, thus generating highly mutagenic covalent crosslinks at the target site whose repair could restore gene function; the number of revertants and spectrum of mutations generated were quantified. Results showed that a phosphoramidate TFO indeed reaches its target sequence, forms crosslinks, and generates mutations at the expected site via a triplex-mediated mechanism: (i) under identical conditions, no mutations were generated by the same TFO at two other loci in the target strain, nor in an isogenic control strain carrying a modified target sequence incapable of supporting triple-helix formation; (ii) for a given target sequence, whether the triplex was formed in vivo on an endogenous gene or in vitro on an exogenous plasmid, the nature of the mutations generated was identical, and consistent with the repair of a psoralen crosslink at the target site. Although the mutation efficiency was probably too low for therapeutic applications, our results confirm the validity of the triple-helix approach and provide a means of evaluating the effectiveness of new chemically modified TFOs and analogs.
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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.