Triplex-forming oligonucleotides (TFOs) are generally designed to inhibit transcription or DNA replication but can be used for more diverse purposes, Here we have designed a hairpin-TFO able to recruit transcription factors to a target DNA, The designed oligonucleotide contains a tripler-forming sequence, linked through a nucleotide loop to a double-stranded hairpin including the SRE enhancer of the c-fos gene promoter, We show here that this oligonucleotide can specifically recognise its DNA target at physiological salt and pH conditions, The stability of the tripler formed under these conditions is very high: >90% of the tripler remains intact after 24 h of incubation. Bound to the double-stranded target DNA, the oligonucleotide retains its ability to interact specifically with transcription factors, recruiting them to the proximity of the target DNA. Our results suggest that this type of oligonucleotide may prove useful in the design of new tools for artificial modulation of gene expression.
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Dublin City Univ, Sch Chem Sci, Dublin 9, Ireland
Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, IrelandDublin City Univ, Sch Chem Sci, Dublin 9, Ireland
McGorman, Brionna
Fantoni, Nicolo Zuin
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Univ Oxford, Chem Res Lab, South Parks Rd, Oxford, EnglandDublin City Univ, Sch Chem Sci, Dublin 9, Ireland
Fantoni, Nicolo Zuin
O'Carroll, Sinead
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Dublin City Univ, Sch Chem Sci, Dublin 9, Ireland
Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, IrelandDublin City Univ, Sch Chem Sci, Dublin 9, Ireland
O'Carroll, Sinead
Ziemele, Anna
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Dublin City Univ, Sch Chem Sci, Dublin 9, Ireland
Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, IrelandDublin City Univ, Sch Chem Sci, Dublin 9, Ireland
Ziemele, Anna
El-Sagheer, Afaf H.
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Univ Oxford, Chem Res Lab, South Parks Rd, Oxford, England
Suez Univ, Fac Petr & Min, Dept Sci & Math, Engn, Suez 43721, EgyptDublin City Univ, Sch Chem Sci, Dublin 9, Ireland
El-Sagheer, Afaf H.
Brown, Tom
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Univ Oxford, Chem Res Lab, South Parks Rd, Oxford, EnglandDublin City Univ, Sch Chem Sci, Dublin 9, Ireland
Brown, Tom
Kellett, Andrew
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Dublin City Univ, Sch Chem Sci, Dublin 9, Ireland
Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland
Dublin City Univ, Sch Chem Sci, Sci Fdn Ireland Res Ctr Pharmaceut, SSPC, Dublin 9, IrelandDublin City Univ, Sch Chem Sci, Dublin 9, Ireland