A Moving Target Gene Therapy: Therapeutic Mechanisms and Strategies

Abstract

Science moves, but slowly slowly, creeping on from point to point.–Alfred Lord Tennyson, 1842Those who toil daily in the labs and clinics of gene therapy, and an impatient public awaiting the fulfillment of many promises, know all too well the truth of Tennyson's words. Those who attempt to put together a textbook on gene therapy, however, must wonder what Tennyson was thinking. Nonetheless, Nancy Smyth Templeton (Baylor College of Medicine in Houston, TX) and Danilo D. Lasic (Liposome Consultations in Newark, CA) have bravely entered the world of scientific textbook publishing by putting together Gene Therapy: Therapeutic Mechanisms and Strategies.Their efforts are largely successful. This is an attractive and comprehensive book, written almost entirely by well-recognized experts in most of the various avenues of inquiry that made up “gene therapy” in the year 2000. The book has 28 well-written chapters divided into four parts: “Viral Delivery and Therapeutic Strategies,” “Nonviral Delivery and Therapeutic Strategies,” “Other Therapeutic Strategies and Regulatory Aspects,” and “Disease Targets and Therapeutic Strategies.” The book is introduced with an interesting foreword by Philip Noguchi of the Food and Drug Administration, who not only applauds the progress made but offers a reminder that the American public is heavily invested in the success of gene therapy and should be considered a full participant in its progress.Templeton and Lasic wisely do not claim to provide the final word. Indeed, they point out that this is the first edition of what they hope will be several, including “frequent updates that will include additional volumes to cover other topics in depth.” This is a good thing as recent advances in gene therapy cannot be covered in a traditional textbook format. Relatively poor sales of gene therapy books don't reflect so much on the words of the writers as they do on the rapidly changing contours of the field.Nevertheless, I find this book amazingly useful and refer to it often in my daily work with the wide range of manuscripts submitted to Molecular Therapy. Although no single chapter goes into the marginalia of its topic, all of them have obviously been written and edited to provide a solid background to the well-informed neophyte and a good review for the more established researcher (and floundering editor). This is no mean task but it is a worthwhile one: many of the books that already exist on various aspects of gene therapy do not provide the same useful and readable focus.Although each section is strong, one can't help but wish for more up-to-date information on topics such as the growing use of lentiviral vectors and HSV amplicons, recent efforts at retargeting adenovirus, and new information and advances in intracellular trafficking of nonviral formulations. Recent disease targets that show some success (e.g., SCID, hemophilia B, Parkinson's in a monkey model) are barely mentioned. Furthermore, it would be good to make sure one of the “future” volumes/updates considers immune system responses to various gene therapy approaches, an area that is rapidly advancing and which has significant implications for the future of gene therapy, particularly in the use of viral vectors. Finally, the chapter on regulatory aspects, while of great interest to many people, could benefit from more practical examples and updates in light of recent changes.The challenge, of course, is to make new information available in an accessible but fast manner. Textbooks can provide the first, but are no good at the second, at least in areas of rapid change. The strengths of the current book as a base could be enhanced by some form of regular electronic “upgrade.” Given both the current turmoil in the field of publishing as a result of rapid electronic advances and the effect of those advances on education, this is an avenue I hope the editors (and their publisher) plan to pursue.One could quibble about less important aspects of this work. Color figures would have helped, particularly in some of the immunohistochemistry photos. In addition, the black and white figures (flowcharts, graphs, etc.) should have been a bit more standardized—some of them look like printouts on an ImageWriter from an old version of MacPaint. A glossary of terms would add value to this book's textbook function. And the “myoblast song,” while pretty darn clever, seems a bit out of place.But these are minor points. A growing number of academic institutions are offering graduate courses in “Gene Therapy 101” and this book is the most solid choice out there for sheer breadth and accessibility of information about a field that may be moving “slowly slowly” to many outsiders, but is racing breathlessly ahead to those inside. It's hard to imagine anyone doing a better job on content: The editors and authors should be commended. They should also be taken up on their request in the Preface for feedback to strengthen future offerings that, it is hoped, will not depend on the creeping of traditional textbook publishing. Science moves, but slowly slowly, creeping on from point to point.–Alfred Lord Tennyson, 1842 Those who toil daily in the labs and clinics of gene therapy, and an impatient public awaiting the fulfillment of many promises, know all too well the truth of Tennyson's words. Those who attempt to put together a textbook on gene therapy, however, must wonder what Tennyson was thinking. Nonetheless, Nancy Smyth Templeton (Baylor College of Medicine in Houston, TX) and Danilo D. Lasic (Liposome Consultations in Newark, CA) have bravely entered the world of scientific textbook publishing by putting together Gene Therapy: Therapeutic Mechanisms and Strategies. Their efforts are largely successful. This is an attractive and comprehensive book, written almost entirely by well-recognized experts in most of the various avenues of inquiry that made up “gene therapy” in the year 2000. The book has 28 well-written chapters divided into four parts: “Viral Delivery and Therapeutic Strategies,” “Nonviral Delivery and Therapeutic Strategies,” “Other Therapeutic Strategies and Regulatory Aspects,” and “Disease Targets and Therapeutic Strategies.” The book is introduced with an interesting foreword by Philip Noguchi of the Food and Drug Administration, who not only applauds the progress made but offers a reminder that the American public is heavily invested in the success of gene therapy and should be considered a full participant in its progress. Templeton and Lasic wisely do not claim to provide the final word. Indeed, they point out that this is the first edition of what they hope will be several, including “frequent updates that will include additional volumes to cover other topics in depth.” This is a good thing as recent advances in gene therapy cannot be covered in a traditional textbook format. Relatively poor sales of gene therapy books don't reflect so much on the words of the writers as they do on the rapidly changing contours of the field. Nevertheless, I find this book amazingly useful and refer to it often in my daily work with the wide range of manuscripts submitted to Molecular Therapy. Although no single chapter goes into the marginalia of its topic, all of them have obviously been written and edited to provide a solid background to the well-informed neophyte and a good review for the more established researcher (and floundering editor). This is no mean task but it is a worthwhile one: many of the books that already exist on various aspects of gene therapy do not provide the same useful and readable focus. Although each section is strong, one can't help but wish for more up-to-date information on topics such as the growing use of lentiviral vectors and HSV amplicons, recent efforts at retargeting adenovirus, and new information and advances in intracellular trafficking of nonviral formulations. Recent disease targets that show some success (e.g., SCID, hemophilia B, Parkinson's in a monkey model) are barely mentioned. Furthermore, it would be good to make sure one of the “future” volumes/updates considers immune system responses to various gene therapy approaches, an area that is rapidly advancing and which has significant implications for the future of gene therapy, particularly in the use of viral vectors. Finally, the chapter on regulatory aspects, while of great interest to many people, could benefit from more practical examples and updates in light of recent changes. The challenge, of course, is to make new information available in an accessible but fast manner. Textbooks can provide the first, but are no good at the second, at least in areas of rapid change. The strengths of the current book as a base could be enhanced by some form of regular electronic “upgrade.” Given both the current turmoil in the field of publishing as a result of rapid electronic advances and the effect of those advances on education, this is an avenue I hope the editors (and their publisher) plan to pursue. One could quibble about less important aspects of this work. Color figures would have helped, particularly in some of the immunohistochemistry photos. In addition, the black and white figures (flowcharts, graphs, etc.) should have been a bit more standardized—some of them look like printouts on an ImageWriter from an old version of MacPaint. A glossary of terms would add value to this book's textbook function. And the “myoblast song,” while pretty darn clever, seems a bit out of place. But these are minor points. A growing number of academic institutions are offering graduate courses in “Gene Therapy 101” and this book is the most solid choice out there for sheer breadth and accessibility of information about a field that may be moving “slowly slowly” to many outsiders, but is racing breathlessly ahead to those inside. It's hard to imagine anyone doing a better job on content: The editors and authors should be commended. They should also be taken up on their request in the Preface for feedback to strengthen future offerings that, it is hoped, will not depend on the creeping of traditional textbook publishing.