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Specific regulation of gene expression by antisense nucleic acids: a summary of methodologies and associated problems.

Gene therapy based on gene-specific nucleic acids has moved from theory to a practical possibility in a very short time. The new DNA and RNA therapeutic reagents are intended to stop the growth of cancerous cells or the production of viruses. At the practical level, the efficacy of antisense oligomers as therapeutic reagents has been carefully examined in various clinical contexts. For the efficient use of antisense nucleic acids as pharmaceutical agents, a complete analysis of their mechanisms of action is necessary. The use of antisense oligomers always involves the following problems: basepair specificity, stereoisomer specificity, stability and resistance to nucleases of sense-antisense duplexes, permeability of the cell membrane and targeting of the oligomer, safety, and the preparation of large amounts of oligomer. Herein, we review the basic concepts and problems associated with the exploitation of antisense technology. We have identified a new transcription factor triple-helix-binding zinc-finger protein-1 (THZif-1) induced by antisense c-myc RNA in the antisense-transformed HL60 cells. The encoded protein functions as the repressor of c-myc to achieve the reduction of the endogenous expression of c-myc gene. Therefore, the introduction of THZif-1 gene into HL60 cells in conjunction with antisense c-myc oligomers may result in the efficient repression of the expression of the c-myc gene. The molecular features of this factor are herein discussed.