Section Review: Biologicals & Immunologicals: Applications of antisense technology to both basic and clinical research

Abstract

Antisense oligodeoxynucleotides (ODNs) are synthetic molecules typically designed to hybridise to the sense strand of the target gene messenger RNA (mRNA). The activity of these molecules reduces gene expression by disrupting the flow of information from gene to protein. The specificity of this interaction arises from the antisense ODN having a unique affinity for the primary sequence of the target gene due to nucleotide base complementarity. Specific inhibition of target gene products allows a rapidly increasing number of researchers to investigate gene function. Additionally, the reversible and specific nature of this interaction has initiated interest in antisense ODNs as a potentially novel class of therapeutics. Antisense molecules are already undergoing clinical trials as candidate therapeutics for several indications. Recent advances in our understanding of the activity of antisense ODNs, together with the advances in ODN chemistry, has made the notion of therapeutically active antisense molecules realistic. However, there remain many challenges in this field which must be overcome. Notably, the most commonly used chemical class of antisense ODNs, the phosphorothioates, has been associated with significant non-specific activities. This brief review aims to present in vivo applications of antisense in the domains of both basic and clinical research.