Antisense Drug Technology: Principles, Strategies and Applications

  • Edited by. Stanley T. Crooke
Marcel Dekker; $225, 916 pp, hardcover, 2001 ISBN 0-8247-0566-1 | ISBN: 0-8247-0566-1

Over the past decade, antisense technology has weathered many of the trials and tribulations facing any new branch of pharmacology, but it is now coming of age. One antisense drug, Isis Pharmaceuticals' (Carlsbad, CA) Vitravene (used topically to treat cytomegalovirus infections in AIDS patients), is already on the market, and that company's recent multimillion-dollar deal with Eli Lilly heralds renewed interest—indeed, restored confidence—in this new technology.

For those keen to get a bird's eye view of the world of antisense, Antisense Drug Technology provide one vantage point. Edited by Stanley Crooke, founder and chief executive officer of Isis Pharmaceuticals and arguably the “father of antisense”, the book covers the basics of the science of antisense, its chemistry, and looks at its potential as a source of new medicines and tools for validating disease targets.

Part I of the book eases the reader in with reviews of the technology of antisense, its chemistry, and its role in target validation. One of the earliest problems for antisense was the need to create molecules that were not degraded in the gut, because DNAs survive only for short periods. Consequently, researchers developed phosphorothioate oligonucleotides incorporating changes to the phosphate backbone.

Part II of the book looks at how these modified oligos have behaved as drugs—their pharmacokinetics and pharmacodynamics—and, as it turned out, also their toxicity. Partly, as a result of the less-than-ideal properties of these molecules, chemists sought to create oligonucleotides with varying chemistries, some of which have profiles more suitable for use as human medicines.

In Part III, authors explain the development and application of further chemical modifications such as peptide nucleic acids (PNAs), locked nucleic acid (LNA), and phosporodiamidate morpholino oligo-mers. A number of chapters in Part III also examine clinical data in support of a role for antisense in the treatment of diseases—from cancers to cardiovascular disease—and their value as experimental tools for the study of other conditions such as inflammation and cardiovascular disease.

As with any attempt to cover a fast-moving area of science, the book will be rather outdated before it reaches the bookshelf, but it should serve as a valuable resource for those interested in how antisense developed to its state today and where it ended up (mostly at Isis Pharmaceuticals, given that around half of the chapters are from Crooke's own staff). Given Isis's domination of the field, perhaps this was unavoidable.

In any case, antisense, it seems, is well on its way to market. In the words of the editor: “Arguably, we are at the end of the beginning of this technology.”