This dissertation describes the development of the TRADE system for directed evolution of the AAV capsid, its successful application to identify the HN1 variant, a novel AAV capsid with enhanced neuronal transduction efficiency and specificity following intravenous vector administration in both rodents and rhesus macaques. This work establishes a novel technology with the potential to facilitate the rapid development of customized AAV vectors targeting cell types of choice and has the potential to significantly impact a wide variety of problems in basic science and medicine where lack of an efficient vector for targeting a critical cell type poses a significant barrier. Thus, TRADE is poised to transform the field of AAV capsid directed evolution.