This paper has been peer reviewed.
ANTISENSE OLIGONUCLEOTIDES: FROM DESIGN TO THERAPEUTIC APPLICATION
Article first published online: 12 MAY 2006
Clinical and Experimental Pharmacology and Physiology
Volume 33, Issue 5-6, pages 533–540, May/June 2006
How to Cite
Chan, J. H., Lim, S. and Wong, W. F. (2006), ANTISENSE OLIGONUCLEOTIDES: FROM DESIGN TO THERAPEUTIC APPLICATION. Clinical and Experimental Pharmacology and Physiology, 33: 533–540. doi: 10.1111/j.1440-1681.2006.04403.x
- Issue published online: 12 MAY 2006
- Article first published online: 12 MAY 2006
- Received 18 October; revision 1 February 2006; accepted 5 February 2006.
- antisense oligonucleotide design;
- cell-penetrating peptide;
- gapmer antisense oligonucleotide;
- locked nucleic acid;
- peptide nucleic acid;
- phosphoroamidate morpholino oligomer;
- RNase H
- 1An antisense oligonucleotide (ASO) is a short strand of deoxyribonucleotide analogue that hybridizes with the complementary mRNA in a sequence-specific manner via Watson–Crick base pairing. Formation of the ASO–mRNA heteroduplex either triggers RNase H activity, leading to mRNA degradation, induces translational arrest by steric hindrance of ribosomal activity, interferes with mRNA maturation by inhibiting splicing or destabilizes pre-mRNA in the nucleus, resulting in downregulation of target protein expression.
- 2The ASO is not only a useful experimental tool in protein target identification and validation, but also a highly selective therapeutic strategy for diseases with dysregulated protein expression.
- 3In the present review, we discuss various theoretical approaches to rational design of ASO, chemical modifications of ASO, ASO delivery systems and ASO-related toxicology. Finally, we survey ASO drugs in various current clinical studies.