Antisense Strategy for Determining Receptor Function

The use of oligonucleotide probes to modulate the synthesis of protein molecules has hadimportant implications in understanding the growth of viruses and expression of oncogenes. Morerecently, antisense strategies have been employed in studies examining the nervous system. Theapplications of this methodology are numerous. Essentially, this technique represents a "knock-out"method by which the endogenous role of particular proteins.can be examined by both in vitro and in vivoinvestigations. We will develop this technology by designing oligonucleotide probes to the serotonin2(5-HT2) receptor which represents a good model in which to define the parameters needed to achievefunctional knockout. The system will be modelled in vitro using homogenous cell cultures expressingthe rat 5-HT2 receptor. Subsequently, effective antisense probes will be administered to whole animalsto determine behavioral and biochemical consequences of 5-HT2 receptor inactivation. The ultimate goalof this approach is to apply the technology to proprietary receptor sites to enable direction ofconventional small molecule drug development by identifying potential therapeutic targets.