Antisense Technology in the Central Nervous System

This book is an excellent survey of the application of antisense technology to studies on the central nervous system. It contains contributions from leading researchers in the field, both from academia and industry. The book is intended for a wide audience, from those with little knowledge of antisense technology, to researchers currently familiar with, and working in, this field. For some reason, many neuroscientists and scientists in the pharmaceutical industry tend to be pessimistic when it comes to the clinical viability of antisense oligonucleotides as drugs. This book rationalizes the usefulness and advantages of antisense oligonucleotides as pharmacological tools and highlights the potential clinical applicability. Antisense Technology in the Central Nervous System is composed of 15 highly diversified chapters. The Introduction, written by the editors, provides a brief overview of subsequent chapters, including the theory, advantages and disadvantages of the technology. Controversial issues, such as cellular uptake and delivery of oligonucleotides, are also covered. Each chapter has a different theme, including optimizing knockdown strategy, the necessity of appropriate controls and what these controls should be, use of antisense administration as a behavioural and electrophysiological tool, antisense mapping, medicinal chemistry, delivery techniques, natural endogenous antisense oligonucleotides, aptamers, ribozymes and antisense gene knockdown. Successful application of antisense oligonucleotides in vivo is challenging and requires careful consideration of a number of experimental details. All chapters identify critical areas in experimental design and in the conduct of in vivo studies to reduce the nonspecific actions of oligonucleotides and enhance the reliability of experiments. There is some redundancy on certain topics, such as testing for antisense specificity and appropriate controls, but, for the most part, each chapter brings new avenues to the reader. One disappointing aspect was that the chapter describing the medicinal chemistry of antisense oligonucleotides did not appear until halfway through the book. This chapter is vital for understanding the basic properties that an effective antisense oligonucleotide should possess. Important information on the varieties of antisense backbone and other modifications, and their advantages, contained in this chapter should have been found earlier in the book. An earlier understanding of the various backbone structures and how these influence biological effects would have enabled the reader to appreciate and critique the experiments described in previous chapters. Perhaps the weakest aspect of the book is the lack of discussion on the toxicity and safety of various oligonucleotides in vivo. Although this topic is addressed briefly in chapter 8, there is no mention of the toxic effects phosphorothioate oligonucleotides possess after delivery into the central nervous system. Straightforward and honest about the limitations and shortcomings of the experimental use of antisense oligonucleotides, several chapters carefully describe the requirements for specificity of action as well as the type of appropriate controls that need to be applied to ensure effects are due to antisense action. These are particularly important issues in this relatively new area of technology, and the repetition in the book is fair warning to the neophyte. Necessarily, some chapters are highly technical. However, most are readable and succeed in explaining the methods to the general reader. Moreover, most chapters include step-by-step protocols for more avid readers who want to implement the techniques and troubleshooting hints, clearly identifying the critical steps for securing reliable results. This book is masterfully thorough, well written and an important read for both skeptics and advocates of antisense technology as it applies to studies on the central nervous system. We commend the editors for formulating an up-to-date book that encompasses such a broad spectrum of the aspects of antisense oligonucleotide technology. Catherine M. Cahill, PhD Montreal, Quebec, Canada James L. Henry, PhD Montreal, Quebec, Canada

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