ABSTRACT
Helping patients by finding new therapeutic agents that specifically reduce the key protein causing the patient’s condition/disease is a major theme in current pharmaceutical discovery and development efforts. The stimulus for this focus is the expectation that as selectivity increases, a greater proportion of the drug in each dose will be bound to the therapeutic target and reduced amounts of drug will be tied up by other proteins. The net effect of increased selectivity, therefore,
should be lower drug doses that are needed to achieve target inhibition and disease improvement, and fewer side effects resulting from suppression of nontarget proteins. With the high selectivity inherent in Watson-Crick hybridization, the use of antisense oligonucleotides (ASOs) has been repeatedly shown to be an effective means for specifically reducing the expression of target mRNA and proteins in numerous in vitro and in vivo model systems. These demonstrations are reviewed extensively in other chapter of this volume and in the previous edition of this book [1].
