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Engineering zinc fingers to target cancer hub genes

Final Report Summary - ZINC-HUBS (Engineering zinc fingers to target cancer hub genes)

Human cells contain thousands of genes that operate in complex networks, communicating by switching each other on or off. In this way, the human body works like a giant genetic computer. Certain genes - called master regulators - are highly connected and control processes involving thousands of other genes. When these hub genes go wrong, for example when they get damaged by mutation, they cause a number of serious diseases, including cancer and diseases of the nerves and brain. The European Research Council funded the Zinc-Hubs project for six years to develop tiny molecular scissors and gene switches - called zinc fingers - to target these master hub genes. The most important result was that we were able to develop zinc fingers to target the genes that go wrong in Huntington's Disease. This fatal disease has no cure and is caused by toxic, sticky proteins building-up in the brain. We were able to design a zinc finger to stop the production of these proteins in cells. Ultimately, the zinc fingers were injected into mice which develop Huntington's disease: we found that a single injection held back symptoms for several weeks. The ERC is now funding further work to develop these zinc fingers as a potential therapy. Overall, the project led to over 15 new peer-reviewed scientific publications including useful new methods in building and controlling genetic networks. More details of the work are available on the research group's website (www.imperial.ac.uk/people/m.isalan).