Towards gene-inhibition therapy: A review of progress and prospects in the field of antiviral antisense nucleic acids and ribozymes

Antisense RNA and its derivatives may provide the basis for highly selective gene inhibition therapies of virus infections. In this review, I concentrate on advances made in the study of antisense RNA and ribozymes during the last five years and their implications for the development of such therapies. It appears that antisense RNAs synthesized at realistic levels within the cell can be much more effective inhibitors than originally supposed. Looking at those experiments that enable comparisons to be made, it seems that inhibitory antisense RNAs are not those that are complementary to particular sites within mRNAs but those that are able to make stable duplexes with their targets, perhaps by virtue of their secondary structure and length. The inclusion of ribozyme sequences within antisense RNAs confers RNA-cleaving activity upon them in vitro and possibly in cells, thereby offering the possibility of markedly increasing their therapeutic potential. The varieties of natural ribozyme and their adaptation as artificial catalysts are reviewed. The implications of these developments for antiviral therapy are discussed.