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The symptoms of FD occur as a result of the accumulation of globotriaosylceramide (Gb3), comprising a substrate of \u03b1\u2010Gal A, in the organs. Adeno\u2010associated virus (AAV)\u2010mediated gene therapy is a promising treatment for FD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>\u03b1\u2010Gal A knockout (GLAko) mice were injected intravenously with AAV2 (1\u2009\u00d7\u200910<jats:sup>11<\/jats:sup> viral genomes [vg]) or AAV9 (1\u2009\u00d7\u200910<jats:sup>11<\/jats:sup> or 2\u2009\u00d7\u200910<jats:sup>12<\/jats:sup> vg) vectors carrying human <jats:italic>GLA<\/jats:italic> (AAV\u2010hGLA), and plasma, brain, heart, liver and kidney were tested for \u03b1\u2010Gal A activity. The vector genome copy numbers (VGCNs) and Gb3 content in each organ were also examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The plasma \u03b1\u2010Gal A enzymatic activity was three\u2010fold higher in the AAV9 2\u2009\u00d7\u200910<jats:sup>12<\/jats:sup> vg group than wild\u2010type (WT) controls, which was maintained for up to 8\u2009weeks after injection. In the AAV9 2\u2009\u00d7\u200910<jats:sup>12<\/jats:sup> vg group, the level of \u03b1\u2010Gal A expression was high in the heart and liver, intermediate in the kidney, and low in the brain. VGCNs in the all organs of the AAV9 2\u2009\u00d7\u200910<jats:sup>12<\/jats:sup> vg group significantly increased compared to the phosphate\u2010buffered\u2010saline (PBS) group. Although Gb3 in the heart, liver and kidney of the AAV9 2\u2009\u00d7\u200910<jats:sup>12<\/jats:sup> vg was reduced compared to PBS group and AAV2 group, and the amount of Gb3 in the brain was not reduced.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Systemic injection of AAV9\u2010hGLA resulted in \u03b1\u2010Gal A expression and Gb3 reduction in the organs of GLAko mice. To expect a higher expression of \u03b1\u2010Gal A in the brain, the injection dosage, administration route and the timing of injection should be reconsidered.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3560","type":"journal-article","created":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T06:30:00Z","timestamp":1688193000000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Therapeutic strategy for Fabry disease by intravenous administration of adeno\u2010associated virus 2 or 9 in \u03b1\u2010galactosidase A\u2010deficient mice"],"prefix":"10.1002","volume":"25","author":[{"given":"Yuka","family":"Hayashi","sequence":"first","affiliation":[{"name":"Division of Genetic Therapeutics, Center for Molecular Medicine Jichi Medical University  Shimotsuke Japan"},{"name":"Department of Neurology Jichi Medical University Saitama Medical Center  Omiya 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