Growth factors in gliomas: antisense and dominant negative mutant strategies

Abstract

Antisense and dominant negative mutant strategies were developed as 'magic bullets' to suppress the function of a particular gene while preserving the remaining cellular activities. While experience with these techniques has dispelled some of the 'magic', these strategies remain useful for understanding the function of particular gene products. Antisense strategies involve the administration of either a synthetic oligodeoxynucleotide or a plasmid construct which produces a sequence that is complementary to the DNA or mRNA of the gene of interest. Antisense binding should inhibit transcription or translation of the gene, and thus decrease synthesis of the protein for which the gene encodes. Conversely, dominant negative mutations inhibit activity of a gene product by encoding for a second protein which suppresses the function of the gene of interest. For example, a single mutant subunit in a multimeric protein might allow normal assembly of the protein while inhibiting its activity. The use of these techniques for investigating the role of various growth factor pathways in glial neoplasia and their potential therapeutic applications are reviewed below.