ArticleProceedings of the National Academy of Sciences of the United States of America2008
Triplex-forming oligonucleotide-orthophenanthroline conjugates for efficient targeted genome modification.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 19 citations in OpenAlex.
- The Development of Non-natural Type Nucleoside to Stabilize Triplex DNA Formation against CG and TA Inversion Site.Current medicinal chemistry · 2024Review
- Modification of the aminopyridine unit of 2'-deoxyaminopyridinyl-pseudocytidine allowing triplex formation at CG interruptions in homopurine sequences.Nucleic acids research · 2018Article
- Oligonucleotide Therapies: The Past and the Present.Human gene therapy · 2015Review
- Zinc-finger nucleases: a powerful tool for genetic engineering of animals.Transgenic research · 2010Review
- Generation of redesigned homing endonucleases comprising DNA-binding domains derived from two different scaffolds.Nucleic acids research · 2010Article
- Efficient targeting of a SCID gene by an engineered single-chain homing endonuclease.Nucleic acids research · 2009Article
- Chromosomal translocations induced at specified loci in human stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Repair of DNA lesions associated with triplex-forming oligonucleotides.Molecular carcinogenesis · 2009Review
Corrections and comments
- Retraction · 2010-02-16Falsification/Fabrication of Data · Investigation by Company/Institution · Unreliable Results and/or Conclusions · · Fabio Cannata named responsible for data falsification
- Retracted
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inefficiency of gene modification by homologous recombination can be overcome by the introduction of a double-strand break (DSB) in the target. Engineering the endonucleases needed, however, remains a challenging task that limits widespread application of nuclease-driven gene modification. We report here that conjugates of orthophenanthroline (OP), a DNA cleaving molecule, and triplex-forming oligonucleotides (TFOs), known to bind specific DNA sequences, are synthetic nucleases efficient at stimulating targeted genome modification. We show that in cultured cells, OP-TFO conjugates induce targeted DSBs. An OP-TFO with a unique target was highly efficient, and mutations at the target site were found in approximately 10% of treated cells, including small deletions most likely introduced during DSB repair by nonhomologous end joining. Importantly, we found that when homologous donor DNA was cotransfected, targeted gene modification took place in >1.5% of treated cells. Because triplex-forming sequences are frequent in human and mouse genes, OP-TFO conjugates therefore constitute an important class of site-specific nucleases for targeted gene modification. Harnessing DNA-damaging molecules to predetermined genomic sites, as achieved here, should also provide inroads into mechanisms of DNA repair and cancer.
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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.