Antisense of oligonucleotides and the inhibition of oncogene expression

Abstract

Inhibition of oncogenes represents a new strategy that might lead to a better understanding of the different steps involved in tumorigenesis and also to the development of new therapeutic approaches. Attempts have been made to interfere with gene expression by in situ generation of mRNA from recombinant vectors (antisense RNA) or by the exogenous introduction of synthetic oligonucleotides (antisense oligonucleotides). Antisense oligonucleotides can inhibit the expression of specific genes by blocking the translation after hybridization with the target mRNAs — the antisense strategy. Antisense oligonucleotides can also be targeted to specific sequences of the DNA double helix. This causes inhibition of transcription — the antigene strategy. Regulatory sequences involved in controlling the transcription of oncogenes are used as targets for this type of ‘antigene’ oligonucleotide. Both strategies can be applied to control the oncogene expression of tumour cells in tissue culture, as exemplified in this review by myc antisense oligonucleotides. Recently the antisense strategy is moving into the area of clinical trials, aimed at curing chronic myelogenous leukaemia by ex vivo bone marrow purging. However, many difficulties have still to be overcome before the application of antisense oligonucleotides can be evaluated in the treatment of cancer.