Control of alternative splicing by antisense oligonucleotides as a potential chemotherapy: effects on gene expression

Expression of alternatively spliced mRNA variants at specific stages of development or in specific cells and tissues contributes to the functional diversity of the human genome. Aberrations in alternative splicing were found as a cause or a contributing factor to the development, progression, or maintenance of various diseases including cancer. The use of antisense oligonucleotides to modify aberrant expression patterns of alternatively spliced mRNAs is a novel means of potentially controlling such diseases. However, to utilize antisense oligonucleotides as molecular chemotherapeutic agents, the global effects of these molecules need to be examined. The advent of gene expression array technology has now made it possible to simultaneously examine changes that occur in the expression levels of several thousand genes in response to antisense treatment. This analysis should help in the development of more specific and efficacious antisense oligonucleotides as molecular therapeutics. (C) 2002 Elsevier Science B.V. All rights reserved.