A valiant effort

Birkhauser Verlag, 1999. DM 198 (xii+379 pages)ISBN 3 7643 5972 2Last year, in a review of the first annual meeting of the American Society of Gene Therapy (Mol. Med. Today, 1998, 4 (9), 374–375), I commented on the diversity of approaches to gene therapy that are currently being pursued. This diversity sets any editor assembling a book on gene therapy an enormous challenge. There is the need to try to reflect the variety of gene transfer systems that are available, the many different disease targets and the various treatment strategies that are being considered. In addition, there is the need to describe research at vastly different stages of development, from early pre-clinical studies through to Phase 2/3 clinical trial. Unfortunately, the recently published Gene Therapy: Principles and Applications fails to rise to this challenge.The development of gene therapy as a field has been dominated by progress in the methods of gene transfer and thus a discussion of the relative merits of each is essential to any gene therapy text. Gene Therapy: Principles and Applications includes three chapters dealing with viral vectors [retroviral, adenoviral and adeno-associated viral (AAV) vectors] and three chapters describing non-viral, physico-chemical methods (cationic lipid and receptor-mediated gene transfer, and particle bombardment). The chapter on particle bombardment is excellent and the Editor should be commended for including this subject when similar texts have often overlooked the area. However, the other chapters, while accurate and generally well written, are not very inspiring and, with the exception of a short section within the adenoviral chapter describing methods for evaluation of bioactivity, rather lacking in practical information. In addition, the lack of chapters covering herpes simplex viral vectors and the application of naked DNA in gene therapy is particular noticeable.The next section encompasses four chapters addressing the gene therapy of single gene defects. The chapters discussing gene therapy for severe combined immunodeficiency (SCID) and cystic fibrosis were excellent choices as research in both of these disease targets has moved from pre-clinical studies to clinical trials, giving the reader a good sense of the process involved. More importantly, the authors of these chapters were also able to hint at how the outcome of these clinical trials is facilitating the development of the next generation of gene transfer delivery systems. The chapters focusing on lysosomal storage disorders and familial hypercholesterolemia (FH) are hampered by the relatively limited number of studies that have been conducted looking at these particular genetic disorders. As the chapter on lysosomal storage disorders concentrated on mouse models of these metabolic disorders, a more general chapter on gene therapy and animal models might have been more useful. This might have facilitated the discussion of gene therapy strategies for other genetic disorders such as muscular dystrophy. Furthermore, a significant proportion of the chapter on FH considered the problems of adenoviral vectors, much of which had been covered in a previous chapter. A chapter examining liver-mediated gene transfer, which would cover FH but also other diseases such as hemophilia, might be of more use to the general reader.The best section in this text is that devoted to gene marking. The three chapters in this section cover the technology and the application of gene marking to hematopoietic cells, and do it well. Studies using gene transfer to hematopoietic cells have not only been pathfinders for gene therapy, as in the case of treatment of the SCID disorder adenosine deaminase deficiency, but have also been critical for the development of novel anti-viral and anti-tumor treatments. In addition, genetic modification of hematopoietic cells has been used to enhance or better understand existing treatment strategy. These diverse applications are well described by the reports in this section. For example, one chapter includes an excellent review of the results from the principal clinical trials attempting to use gene marking to understand further the process of engraftment following autologous bone marrow transplantation (AuBMT). The authors clearly describe the results from the published trials, in particular explaining the possible reasons for the huge variation in gene-marking frequencies seen in these studies and what this may mean for the optimization of AuBMT, an important element of many cancer therapies.The final section covers the gene therapy approaches to the treatment of cancer. These chapters include more-specific data than the other chapters but generally include sufficient background information for the reader to put this into context with the results from other laboratories. Two chapters sit rather oddly in this section; one describes the identification of tumor antigens and the other peptide vaccinations. Both chapters are good but do not seem appropriate to the general thrust of this book. Otherwise, many of the treatment strategies being applied to gene therapy of cancer are covered, including antisense approaches, immunomodulation and tumor cell killing using pro-drug activation.The technology underlying the field of gene therapy is developing at an ever-increasing rate, immediately putting any book with its relatively long production time at a disadvantage. As a consequence, some major developments in the past two years are not covered in this text; the generation of helper-dependent or ‘gutless’ adenoviral vectors and lentiviral vectors are just two examples. Individual chapters will be of use to those wishing to familiarize themselves with specific topics. In fact, treating this text as a collection of individual essays is perhaps the most rewarding approach to this book.There is minimal standardization of the layout of each chapter; and the variation in citation and bibliography format is particularly annoying. Gene Therapy: Principles and Applications is a valiant effort at trying to cover the very wide-ranging field of gene therapy; however, there is too much repetition and too many gaps for it to be more than the occasional reference text. Unfortunately, there isn’t really anything better at the moment: although several other general texts are due for publication in the new future, in the meantime up-to-date reviews within main-stream journals will be more useful in this rapidly changing field.