DNA ANTISENSE STRATEGIES IN THE STUDY OF RECEPTORS FOR VASOACTIVE PEPTIDES, AND OF GROWTH AND WOUND-HEALING FACTORS

Antisense oligodeoxynucleotide technology has contributed greatly to t he overall understanding of both mRNA stability as well as translation al processes leading to protein synthesis. Arrest of translational pro cesses by DNA antisense strands usually reduces maximal effects of ago nists without affecting their apparent affinities in treated isolated vascular or nonvascular preparations. In the present study, examples a re given of DNA antisense oligonucleotide-induced repression of recept ors for endothelins, kinins as well as of the platelet-derived growth factor. Furthermore, the efficiency of this technology illustrates the roles of protooncogenes (c-myc and c-myb) in wound-healing mechanisms . The overall mechanism of action of these oligomers is described and the relevance of size, chemical alterations and mode of delivery are i llustrated. Release of oligophosphorothioates from polymer matrices an d gels can produce a prolonged effect in vivo. Antisense oligonucleoti des remain essential in experimental models for which receptor antagon ists or selective inhibitors of intracellular components are currently unavailable.