Antisense and antigene oligonucleotides: Structure, stability and delivery

Diseases are being understood and treated at an increasingly higher level of genetic order and function. Recent advances in nucleic acid-based therapeutics offer great hope in controlling sequence-specific aberrant gene expression at the level of transcription or translation. Oligonucleotides (ODNs) which control gene expression at translation levels are known as antisense ODNs, whereas those act at transcriptional levels are triplex-forming oligonucleotides (TFOs), called anti-gene strategy (Figure 19.1). There has been tremendous progress in the understanding and application of antisense ODNs since first proposed in 1978 by Zamecnik and Stephenson. A number of different ODNs have been in clinical trials against many diseases, such as human immunodeficiency virus HIV infections and cytomegalovirus (CMV) ocular infections as well as in the control of hematological disorders including Crohn’s disease. Several antisense ODN-based formulations are in clinical trials and there is already one FDA approved product for the treatment of human CMV-induced retinitis. However, triplex forming oligonucleotides (TFOs), which can inhibit gene transcription are quite promising antigene therapy for modulation of gene expression.