“…Irreversible modifications of DNA have indeed been described when TFOs attached to a reactive molecule are provided with optimal conditions for activity of these chemical reagents, leading to covalent modification of the bases or cleavage of the backbone on the target DNA. A wide range of reactive groups, including photo‐inducible crosslinkers (Psoralen), alkylating groups (nitrogen mustard), and cleaving agents (EDTA and orthophenanthroline), have been covalently linked to TFOs in attempt to render their chemical action specific to the DNA sequence recognised by the oligonucleotide (for a review see30) (Figure 3). …”
Section: Triple Helix Formation: From Formation To Irreversibilitymentioning
The ability to specifically manipulate gene expression has wide-ranging applications in experimental biology and in gene-based therapeutics. The design of molecules that recognise specific sequences on the DNA double helix provides us with interesting tools to interfere with DNA information processing at an early stage of gene expression. Triplex-forming molecules specifically recognise oligopyrimidine-oligopurine sequences by hydrogen bonding interactions. Applications of such triplex-forming molecules (TFMs) are the subject of the present review. In cell cultures, TFMs have been successfully used to down- or up-regulate transcription in a gene-specific manner and to induce genomic DNA modifications at a selected site. The first evidence of a triplex-based activity in animals has been provided recently. In addition, TFMs are also powerful tools for gene-specific chemistry, in particular for gene transfer applications.
“…Irreversible modifications of DNA have indeed been described when TFOs attached to a reactive molecule are provided with optimal conditions for activity of these chemical reagents, leading to covalent modification of the bases or cleavage of the backbone on the target DNA. A wide range of reactive groups, including photo‐inducible crosslinkers (Psoralen), alkylating groups (nitrogen mustard), and cleaving agents (EDTA and orthophenanthroline), have been covalently linked to TFOs in attempt to render their chemical action specific to the DNA sequence recognised by the oligonucleotide (for a review see30) (Figure 3). …”
Section: Triple Helix Formation: From Formation To Irreversibilitymentioning
The ability to specifically manipulate gene expression has wide-ranging applications in experimental biology and in gene-based therapeutics. The design of molecules that recognise specific sequences on the DNA double helix provides us with interesting tools to interfere with DNA information processing at an early stage of gene expression. Triplex-forming molecules specifically recognise oligopyrimidine-oligopurine sequences by hydrogen bonding interactions. Applications of such triplex-forming molecules (TFMs) are the subject of the present review. In cell cultures, TFMs have been successfully used to down- or up-regulate transcription in a gene-specific manner and to induce genomic DNA modifications at a selected site. The first evidence of a triplex-based activity in animals has been provided recently. In addition, TFMs are also powerful tools for gene-specific chemistry, in particular for gene transfer applications.
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