The use of classical, germ-line genetics to define gene function in vertebrates is severely limited by embryonic lethality, developmental compensation and adaptive functional degeneracy, all of which obscure the roles played by genes in adult tissues that would normally have developed in the presence of that gene. Consequently, classical germ line knock-out technologies provide only limited information as to the roles of genes in adult tissues and their pathologies. Nowhere is this limitation more profound than in our understanding of cancers, diseases that arise in the main through genetic accidents in established adult tissues and in which defining the ongoing roles of specific genes in maintenance of established tumours is crucial for identifying targets for therapeutic intervention. We will develop a suite of novel technologies for “kinetic genetics” – the rapid and reversible inhibition of specific genes in adult mice, either systemically or in specific tissues. These technologies will not only provide invaluable and novel information concerning gene function in adult tissues but we will use them specifically to define which components of oncogenic networks make the best targets for future cancer therapy.
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