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These vectors include adeno\u2010associated viruses, adenoviruses, herpes viruses, rhabdoviruses and others. However, these naturally occurring viruses lack inherent tissue or organ tropism for tailored disease treatment. To address this, we devised an optimized process involving directed viral capsid evolution, organ\u2010specific humanized mouse models and in vitro\u2010in vivo virus screening. Our approach allows for the rapid generation specifically modified adeno\u2010associated virus variants, surpassing the time required for natural evolution, which spans millions of years. Notably, these variants exhibit robust targeting of the liver, favouring chimeric human liver cells over murine hepatocytes. 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