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One believer in “nanomedicine” is James Baker, chief of the allergy and immunology department at the University of Michigan’s Medical School. He might seem an unlikely champion of nanotech in medicine, a field that has more often been associated with sci-fi notions of tiny machines cruising the human body than with clinically feasible treatments. But Baker is convinced that the tools of nanotechnology will eventually provide a far safer and more effective way to repair genes. So convinced, in fact, that last year Baker founded the University of Michigan’s Center for Biologic Nanotechnology, bringing doctors and medical researchers together with chemists and engineers to turn nanomedicine from a futurist dream into clinical reality.

For Baker, the attraction to nanostructures is that these nonbiological substances can be constructed so that they will not trigger an immune response. Years of immunology research has convinced Baker that viral methods are fraught with trouble, because of the severe immune reaction they trigger. “That started me thinking about synthetic systems,” says the Michigan immunologist. In particular, Baker began to wonder if a novel type of polymer called dendrimers-tree-shaped synthetic molecules that can be engineered on a nanometer scale-could be used to slip DNA covertly through immune defenses into target cells. Dendrimers were invented two decades ago by Baker’s colleague and scientific director of the new center, polymer chemist Donald Tomalia. Since then, dendrimer research has exploded, with researchers pursuing applications from drug delivery to medical imaging.

What sets dendrimers apart from other polymers is their precise nanostructure. Dendrimers form nanometer by nanometer, so the number of synthetic steps dictates their exact size. Their surfaces can be made to form a dense field of molecular groups that serve as hooks for attaching other useful molecules. Dendrimers can also carry internal molecular baggage. These properties could make dendrimers excellent transporters for sneaking DNA into cells. Scientists decorate the dendrimer molecule with the DNA, which scrunches down on the polymer’s surface. The dendrimer-DNA bundles are injected into the tissue; dendrimers of just the right size trigger a process called endocytosis in which the cell deforms to let the DNA-dendrimer package in. Once inside, the DNA is released and migrates to the nucleus where it becomes part of the cell’s genome.

While the research is still in its early stages, initial results suggest that these synthetic nanomaterials just might be a safer alternative to viral transporters for gene therapy. So far, building on work done at the University of California, San Francisco, in the early 1990s, Baker and his Michigan colleagues have shown in lab experiments that they can use dendrimers to efficiently transfer DNA into the cell’s genes. They are now conducting animal trials with rats and mice to demonstrate that the dendrimers don’t cause toxic side effects and to see exactly how efficient dendrimers can be. The next step will be to carry out similar studies in humans to assess the promise of dendrimers for fixing genes. Then the arduous process of setting up actual experiments must begin, involving approval by a special advisory committee at the National Institutes of Health and the Food and Drug Administration. With perseverance, Baker hopes to see clinical trials of dendrimer gene therapy in two years.

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