Antisense RNA gene therapy for studying and modulating biological processes

Agents that produce their effects through an antisense mechanism offer the possibility of developing highly specific alternatives to traditional pharm acological antagonists, thereby providing a novel class of therapeutic agen ts, ones which act at the level of gene expression. Among the antisense com pounds, antisense RNA produced intracellularly by an expression vector has been used extensively in the past several years. This review considers the advantages of the antisense RNA approach over the use of antisense oligodeo xynucleotides, the different means by which one may deliver and produce ant isense RNA inside cells, and the experimental criteria one should use to as certain whether the antisense RNA is acting through a true antisense mechan ism. Its major emphasis is on exploring the potential therapeutic use of an tisense RNA in several areas of medicine. For example, in the field of onco logy antisense RNA has been used to inhibit several different target protei ns, such as growth factors, growth factor receptors, proteins responsible f or the invasive potential of tumor cells and proteins directly involved in cell cycle progression. In particular, a detailed discussion is presented o n the possibility of selectively inhibiting the growth of tumor cells by us ing antisense RNA expression vectors directed to the individual calmodulin transcripts. Detailed consideration is also provided on the development and potential therapeutic applications of antisense RNA vectors targeted to th e D2 dopamine receptor subtype. Studies are also summarized in which antise nse RNA has been used to develop more effective therapies for infections wi th certain viruses such as the human immunodeficiency virus and the virus o f hepatitis B, and data are reviewed suggesting new approaches to reduce el evated blood pressure using antisense RNA directed to proteins and receptor s from the renin-angiotensin system, Finally, Eve outline some of the probl ems which the studies so far have yielded and some outstanding questions wh ich remain to be answered in order to develop further antisense RNA vectors as therapeutic agents.