Antisense strategies in neurobiology

Abstract

The use of antisense oligodeoxynucleotides, targeted to the transcripts encoding biologically active proteins in the nervous system, provides a novel and highly selective means to further our understanding of the function of these proteins. Recent studies of these agents also suggest the possibility of their being used therapeutically for a variety of diseases involving neuronal tissue. In this paper we review studies showing the in vitro and in vivo effects of antisense oligodeoxynucleotides as they relate to neurobiological functions. Particular attention is paid to the behavioral and biochemical effects of antisense oligodeoxynucleotides directed to the various subtypes of receptors for the neurotransmitter dopamine. An example is also provided showing the effects of a plasmid vector expressing an antisense RNA targeted to the calmodulin mRNAs in the PC12 pheochromocytoma cell line. The advantages of antisense oligodeoxynucleotides over traditional pharmacological treatments are assessed, and the advantages of using vectors encoding antisense RNA over the use of antisense oligodeoxynucleotides are also considered. We also describe the criteria that should be used in designing antisense oligodeoxynucleotides and several controls that should be employed to assure their specificity of action.