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Self-assembling Complexes for Gene Delivery
  1. A Parker

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    Kabanov AV, Felgner PL, Seymour LW, eds. (£70.00.) Wiley, 1998. ISBN 0471 97269

    This publication brings together a collective wealth of knowledge from a number of experts in the field of non-viral gene therapeutics, and addresses the hurdles and most recent progresses in the field. The book is divided into a user friendly series of subsections, beginning with an extensive outline of the principles of self assembly of DNA with cationic agents, such as lipids or polyamino acids, right through to some of the ongoing clinical evaluations of the formulations currently in trials.

    Although the reader might become bogged down in the convoluted theories of complexation, and the mathematics governing self assembly outlined in the first part of the book, the chapters are all well referenced, and the discerning reader will be directed towards further literature as necessary. The second part of the book provides an excellent synopsis of natural mechanisms for the delivery of foreign DNA. Endocytosis is comprehensively reviewed, followed by an especially interesting insight by Greber into the differing mechanisms used by a range of animal viruses to deliver their DNA to the nucleus of the eukaryotic cell, and the possible pathways that could be hijacked by gene delivery complexes to achieve the same result.

    The ensuing subsections of the book outline recent experimental observations using various different formulations of gene delivery complexes. Extensive insights into the behaviour of lipoplexes, polyplexes, and dendrimers (parts 3 and 4) both in vitro and in vivo are reviewed, with the modality of action for thedifferent formulations also thoroughly scrutinised. However, little, if any, mention is made of recent advances in the delivery of naked DNA and the use of electroporation and ultrasound in directing DNA delivery.

    Part 5 reviews the pharmacokinetics of macromolecules and gene delivery systems. This is a key issue for all gene delivery constructs because it is essential that the agent is retained systemically for a long enough time for it to reach its site of action. This is an area that has seen important advances in recent years yet is only reviewed briefly here. However, the interested reader is again guided to a wealth of further reading that provides additional insights.

    Subsection 6 gives an extensive summary of the use of ligands and peptides to promote cell entry of complexes, with particular emphasis on (receptor) binding ligands and agents that promote the release of DNA either by endosome membrane disruption or vector unpackaging. This is followed by a briefsubsection outlining some novel construct formulations encompassing semisynthetic vectors (combining viral proteins with non-viral vectors) and systems for sustained release of gene delivery systems.

    The book concludes with an appraisal of the non-viral gene delivery vectors in trials, evaluating their use in the treatment of the monogenetic disorder, cystic fibrosis, and moving on to their potential in cancer treatment. Although this section is somewhat out of date (given the ever increasing number of trials in progress), it still provides the reader with an invaluable insight into the progression of non-viral gene delivery vectors from the laboratory into the clinic.

    On the whole, this book provides an exceptional insight into its subject area, and offers good value for money. I would certainly recommend this book to those with an interest in this field of study.

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