Prospects for the Therapeutic Use of Antigene Oligonucleotides
作者:
MaherL. James,
期刊:
Cancer Investigation
(Taylor Available online 1996)
卷期:
Volume 14,
issue 1
页码: 66-82
ISSN:0735-7907
年代: 1996
DOI:10.3109/07357909609018437
出版商: Taylor&Francis
数据来源: Taylor
摘要:
An outgrowth of classic nucleic acid interaction studies, oligonucleotide-directed triple helix formation is a unique method for creating highly specific chemical ligands that recognize and bind to particular sequences of duplex DNA. Under permissive conditions, these oligonucleotide-based compounds can approach or exceed the binding affinity and sequence specificity of natural DNA-binding proteins. Triple helix recognition has been found to be useful in certain cell-free applications including precise chromosome fragmentation. It has been proposed that such oligonucleotides could also form the basis for gene-targeted (antigene) drugs that might repress transcription from undesired genes in living cells. However, current strategies for oligonucleotide-directed triple helix formation suffer from important constraints involving requirements for stabilizing binding conditions, restrictions on permitted target sequences, and inefficient nuclear delivery of oligonucleotides. Implementation of oligonucleotide-directed triple helix formation as a viable approach to cancer therapy must therefore await clever solutions to a series of fascinating problems.
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