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It can manifest with severe neurodegeneration and visceral pathology. The most acute neuronopathic form (nGD), for which there are no curative therapeutic options, is characterised by devastating neuropathology and death during infancy. In this study, we investigated the therapeutic benefit of systemically delivered AAV9 vectors expressing the human GBA1 gene at two different doses comparing a neuronal-selective promoter with ubiquitous promoters. Our results highlight the importance of a careful evaluation of the promoter sequence used in gene delivery vectors, suggesting a neuron-targeted therapy leading to high levels of enzymatic activity in the brain but lower GCase expression in the viscera, might be the optimal therapeutic strategy for nGD.<\/jats:p>","DOI":"10.1093\/hmg\/ddae081","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T08:51:27Z","timestamp":1715935887000},"source":"Crossref","is-referenced-by-count":4,"title":["Comparison of different promoters to improve AAV vector-mediated gene therapy for neuronopathic Gaucher disease"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5986-6082","authenticated-orcid":false,"given":"Giulia","family":"Massaro","sequence":"first","affiliation":[{"name":"UCL School of Pharmacy, University College London , 29-38 Brunswick Square, London, WC1N 1AX , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy F","family":"Geard","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London , 29-38 Brunswick Square, London, WC1N 1AX , United Kingdom"},{"name":"Wits\/SAMRC Antiviral Gene Therapy Research Unit , Faculty of Health Sciences, University of the Witwatersrand Medical, School, 7 York Road, Parktown 2193 , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemanth R","family":"Nelvagal","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London , 29-38 Brunswick Square, London, WC1N 1AX , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Gore","sequence":"additional","affiliation":[{"name":"Apollo Therapeutics , Stevenage Bioscience Catalyst, 50-60 Station Road, Cambridge, CB1 2JH , United 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