Recipes for ribozyme therapy: Therapeutic Applications of Ribozymes edited by K.J. Scanlon

Abstract

Humana Press, 1998. Hardback US$79.50 (xiv+462 pages)ISBN 0 89603 477 1It was only in the early 1980s that the first catalytic RNA molecules (ribozymes) were identified. A few years later, the book Therapeutic Applications of Ribozymes has been published and contains ‘recipes’ for gene therapy. It is quite amazing really. On the other hand, why be amazed? The principle is so simple; if the sequence of a target gene is known then ribozymes can be designed to downregulate its expression. This book is an excellent source of experimental protocols designed to downregulate the expression of several disease-associated genes.Ribozymes are rare RNA molecules that can be tailored to cleave or splice other RNA molecules; they can thus be used to interfere with gene expression through targeted RNA manipulation. After their identification, research focused on determining ribozyme structure and mechanism of action. However, the ultimate aim has always been to use ribozymes as trans-acting therapeutic and diagnostic tools. A lot of ground has been covered since then, and we now have a very good idea how these special RNA molecules work. Moreover, there is great optimism that ribozymes can be used to treat a variety of diseases. Ribozymes offer the advantage of being easy to design and construct and can act specifically against their target RNA. The main emphasis of this book is on the trans-cleaving, and especially hammerhead, ribozymes, which have dominated ribozyme research on downregulating gene expression.A particularly important task in achieving the successful downregulation of gene expression is to deliver and express ribozymes efficiently. Therapeutic Applications of Ribozymes is a rich resource of ribozyme-delivery protocols. Although most of these protocols are within the context of various chapters, they can be adapted for other experimental purposes. Several of these protocols describe the transfer of ribozymes into cells and organisms by using viral (retroviral, adenoviral, adeno-associated viral) vectors and liposome-based carriers.Although the spectrum of diseases described in this book is wide, the majority of chapters are devoted to the ribozyme-mediated inhibition of viral infections and cancer. More specifically, authors describe, in detail, protocols to downregulate viral gene expression, for example, in HIV, hepatitis B virus and bovine leukemia virus. There has been much progress in the application of ribozymes to HIV, and it is interesting to see a chapter in the book by E.M. Poeschla and co-workers that describes how HIV can be targeted using ribozyme vectors from freshly isolated human peripheral blood T cells. Several chapters also describe the use of ribozymes to inhibit tumorigenesis. In most of these cases, the book refers to the design of hammerhead ribozymes to target ras mutations that occur in several types of cancer.Although the main emphasis of the book is to describe ways in which trans-cleaving ribozymes can tackle diseases, the editor has cleverly managed to include a few more technical chapters that instruct the reader on how to design and construct ribozymes. It would have been useful if additional and more general technical chapters had been included in the book as many readers will be interested in the therapeutic technology of ribozymes and not necessarily in the therapy of the outlined diseases.The chapters are well written and most of them stand alone, independent of the remainder of the book. Extensive reference lists are provided in many chapters so that the reader can obtain additional information. Moreover, the experimental protocols are detailed and self-contained and can be performed by scientists who do not have prior experience in ribozyme technology. An excellent feature of this book is the widely applicable methodology that is described. Protocols can be applied to all experimental levels (cell-free systems, cell culture and higher organisms), which makes the book attractive to a wide range of readers.Therapeutic Applications of Ribozymes is a very useful book that combines important theoretical and practical information and is applicable to students, clinicians and scientists who are interested in ribozyme technology and/or the downregulation of a particular gene. Furthermore, this book is useful to scientists who are already in the ribozyme field as it provides many alternative ideas and protocols. As the editor concludes in the preface, ‘Ribozyme technology has rapidly matured to allow its entrance into the clinical arena.’ This book is a wealthy resource full of protocols on how trans-cleaving ribozymes can be used as therapeutic tools and is highly recommended.