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Control of gene expression by oligonucleotides : antisense and triple helix strategies


Hématologie. Volume 3, Number 5, 451-64, Septembre-Octobre 1997, Thérapeutiques biotechnologiques

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Author(s) : Anne-Laure Guieysse-Peugeot, Thérèse Garestier, Claude Hélène

Summary : New therapeutic approaches are developped using synthetic oligonucleotides to control the expression of specific genes. When targeted to messenger RNAs, oligonucleotides inhibit translation, this is the antisense strategy. Oligonucleotides can also be targeted to a specific sequence of the double stranded DNA and form a local triple helix that can inhibit transcription, this is the antigene or triple helix strategy. Significant efforts are directed toward development of chemically modified oligonucleotides that resist to nuclease degradation. Carriers are developped for specific and efficient oligonucleotide delivery to target cells and to the desired intracellular compartment. Both approaches can be applied to specifically control the oncogene expression in tumor cells in vitro and, for antisense, in vivo in animal tumor models. Clinical trials are in progress using antisense oligonucleotides targeted to different viral and cellular genes (CMV, HIV, ICAM-1, PKC alpha, c-raf kinase, myc).

Keywords : antisense, triple helix, oligonucleotide, control of gene expression.

 

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