ANTISENSE TECHNOLOGY - PROSPECTS FOR TREATMENT OF NEUROPSYCHIATRIC DISORDERS

Antisense oligodeoxynucleotides (ODN) are short (15 to 30 bases) molecules of synthetic single-stranded DNA, complementary to strategically chosen sequences within a target messenger RNA (mRNA). Theoretical considerations and evidence obtained in tissue culture systems have long suggested the usefulness of this class of compounds for blocking the expression of specific gene products. However, antisense ODN had limitations that were likely to reduce their application outside the limited field of cellular in vitro studies. These limitations include problems of cellular uptake and in vivo stability, and high cost of synthesis. The automation of ODN synthesis has dramatically reduced the costs of production. This has led to a rapidly growing number of recent reports that have suggested potential uses for these agents. Emerging applications include their use as novel pharmacological tools in animal studies of brain systems thought to be involved in the pathophysiology of psychiatric and neurological disorders. While there are many obstacles to be overcome before antisense ODN can be considered as therapeutic agents, suggested future applications include the treatment of ischaemic brain damage, schizophrenia, anxiety and drug abuse.