In the early 90’s, gene therapists were beginning to get their heads around the concept of targeted delivery as a means to improve safety and efficacy of gene therapy. Retroviral vectors were, at that time, the most promising vehicles for gene delivery, having been successfully used in the first clinical trials. Naturally, the targeting of retroviral vectors was at the forefront of research, in particular at the level of infection as pointed out in one of the first reviews on this area written by Walter Gunzburg and myself and appearing in Human Gene Therapy. Although an important new concept at the time, it all turned out to be a lot more complicated from today’s standpoint.
The modification of virus envelopes fascinated John Dangerfield – he saw viruses as boats that could be equipped with off board ATP driven motors or magnetised by the attachment of iron particles. All very science fiction, I thought, a sort of minaturised lego or mechano set enabling functionalised viruses to be steered so that they deliver their cargo of therapeutic genes to distant ports of damaged or defective cells in the body. Of course, the overriding problem was how to attach these molecules to the virus membrane...
Fast forward to today, and we have a book edited by John and former student and colleague Christoph Metzner, about GPI membrane anchors, a molecular tag that helps insert proteins into the plasma membrane of cells and not just anywhere but in so called lipid rafts, agglomerations or islands of lipid that float in the plasma membrane. The book covers a wide variety of aspects of GPI anchors, what they are, their structure, how they function, what roles they carry out, how they can be used as a tool in biotechnology and how similar GPI-like molecules can be created by molecular mimicry. John and Christoph have selected some of the world’s foremost authorities on GPI anchors to contribute chapters to this book. These highly skilled authors provide not only reviews of the knowledge that has been gained about GPI anchors over the last decade or two but also protocols on how to isolate and modify such molecules. Thus the book can be viewed as a nuts and bolts engineering manual and cook book – a kind of “all you ever wanted to know” guide. All in all, the authors have made excellent selections showcasing various facets of current GPI research and shown remarkable editorial skills as well as contributing significant progress themselves to this field.
So why start this foreword with ruminations about the targeting of enveloped viruses like retroviruses? Well GPI anchors offer a solution for the insertion of all kinds of proteins into the plasma membrane not only of cells but also of enveloped viruses and that offers a means to attach ATP motors, magnetic particles and almost any other nanomolecule. This technology, which has been termed “virus painting”, but can also be viewed as a type of decorating or coating of enveloped virions, holds much promise for the targeting of safer virus vectors and vaccines as well as having uses in the diagnosis of well-known and emerging virus diseases.
Dr. Brian Salmons, President and CEO of SGAUSTRIA