ABSTRACT
The ‘antisense’ concept (Zamecnik and Stevenson, 1978) is 20 years old and is still a rational and promising approach in developing oligonucleotides or analogues as therapeutic agents, with potential applications in oncology, in viral diseases and in gene-related disorders. These potential drugs have captured the imagination, since the compounds are rationally designed with supposedly high specificity to interfere with genetic information, from the gene to the protein, by intermediary alteration of RNA metabolism. In the past five years, we have learned a lot-but still not enough-on the fate of this new class of compounds, from basic interactions with their putative targets to tolerance and efficacy clinical trials in humans, through preclinical studies in animal models, in terms of pharmacokinetics and pharmacodynamics.
