Antisense phosphorothioate oligodeoxynucleotides: introductory concepts and possible molecular mechanisms of toxicity

Toxicology Letters
G Zon

Abstract

Over the past 5 years or so, much attention has been given to the possible use of synthetic antisense oligonucleotide analogs as a new class of therapeutic agents that function by sequence-specific inhibition of genetic expression. The basic design concepts which underline this novel approach to drug discovery are briefly described herein, together with some of the chemical, biochemical, and pharmacological aspects of phosphorothioate oligodeoxynucleotides that are first-generation antisense compounds now under clinical investigation. Possible molecular mechanisms of toxicity for this class, and other structural types of antisense compounds are discussed with the hope of stimulating interest in future toxicological studies in this emerging area of drug development.

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