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Towards the targeted modulation of gene expression by modified triplex-forming oligonucleotides

Towards the targeted modulation of gene expression by modified triplex-forming oligonucleotides
Towards the targeted modulation of gene expression by modified triplex-forming oligonucleotides
DNA triple helices are formed when a third nucleic acid strand binds within the major groove of a DNA duplex. The formation of these structures can be used to achieve selective recognition of extended DNA sequences, which may be useful in several medical and biotechnological applications. Although triplex formation is relatively straightforward in vitro, there are several problems that limit its use in cellular contexts, including a low stability at physiological pH and a requirement for oligopurine.oligopyrimidine target sites. There are also concerns about the uptake, localisation and degradation of triplex-forming oligonucleotides (TFOs) in cells, as well as the accessibility of chromosomal DNA. Major advances in the chemistry of DNA triplex formation have been made in the last few years and this review highlights the current status of this approach, with an emphasis on the use of chemically modified TFOs for gene targeting.
DNA sequences, transcription initiation, gene expression, yeast systems, parallel triplexes
1872-3136
1-10
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Rusling, David A.
d08f1f97-f8a9-4980-a025-ae41c23a938f
Broughton-Head, Victoria J.
d094aa77-c889-4747-84d2-55542805c67c
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Rusling, David A.
d08f1f97-f8a9-4980-a025-ae41c23a938f
Broughton-Head, Victoria J.
d094aa77-c889-4747-84d2-55542805c67c
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89

Fox, Keith R., Rusling, David A., Broughton-Head, Victoria J. and Brown, Tom (2008) Towards the targeted modulation of gene expression by modified triplex-forming oligonucleotides. Current Chemical Biology, 2 (1), 1-10. (doi:10.2174/187231308783334135).

Record type: Article

Abstract

DNA triple helices are formed when a third nucleic acid strand binds within the major groove of a DNA duplex. The formation of these structures can be used to achieve selective recognition of extended DNA sequences, which may be useful in several medical and biotechnological applications. Although triplex formation is relatively straightforward in vitro, there are several problems that limit its use in cellular contexts, including a low stability at physiological pH and a requirement for oligopurine.oligopyrimidine target sites. There are also concerns about the uptake, localisation and degradation of triplex-forming oligonucleotides (TFOs) in cells, as well as the accessibility of chromosomal DNA. Major advances in the chemistry of DNA triplex formation have been made in the last few years and this review highlights the current status of this approach, with an emphasis on the use of chemically modified TFOs for gene targeting.

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More information

Published date: January 2008
Keywords: DNA sequences, transcription initiation, gene expression, yeast systems, parallel triplexes

Identifiers

Local EPrints ID: 142591
URI: http://eprints.soton.ac.uk/id/eprint/142591
ISSN: 1872-3136
PURE UUID: 685ab462-e6a4-4944-853c-246112edad40
ORCID for Keith R. Fox: ORCID iD orcid.org/0000-0002-2925-7315
ORCID for David A. Rusling: ORCID iD orcid.org/0000-0002-7442-686X

Catalogue record

Date deposited: 01 Apr 2010 15:20
Last modified: 14 Mar 2024 02:33

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Contributors

Author: Keith R. Fox ORCID iD
Author: David A. Rusling ORCID iD
Author: Victoria J. Broughton-Head
Author: Tom Brown

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