{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T20:51:38Z","timestamp":1761511898786},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,11,5]],"date-time":"2003-11-05T00:00:00Z","timestamp":1067990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2004,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Fabry disease is a recessive, X\u2010linked disorder caused by a deficiency of the lysosomal enzyme \u03b1\u2010galactosidase A, leading to an accumulation of the glycosphingolipid globotriaosylceramide (GL\u20103) in most tissues of the body. The goal of this study was to determine if systemic delivery of a nonviral vector could correct the enzyme deficiency and reduce the levels of GL\u20103 in different tissues of a transgenic knockout mouse model of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cationic lipid was complexed with a CpG\u2010depleted plasmid DNA vector and then injected intravenously into Fabry mice. The levels of \u03b1\u2010galactosidase A and GL\u20103 in different tissues were assayed at various time points after injection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Expression of \u03b1\u2010galactosidase A was detected in the different tissues of Fabry mice for up to 3 months after complex administration, but resulted in minimal reductions in GL\u20103 levels. However, the use of the anti\u2010inflammatory drug dexamethasone and multiple dosing increased \u03b1\u2010galactosidase A expression and resulted in significant reductions of GL\u20103 in all the organs with the exception of the kidney. In addition, injecting complex into young Fabry mice partially prevented the normal accumulation of GL\u20103 in the heart, lung, and liver.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Systemic delivery of a cationic lipid\u2013pDNA complex partially corrected the enzyme deficiency and reduced glycolipid storage in a mouse model of Fabry disease. The results are one of the few demonstrations of long\u2010term efficacy in a genetic disease model using nonviral vectors. However, substantial improvements in expression, especially in critical organs such as the kidney, are required before these vectors can become a viable approach to treat Fabry disease and other lysosomal storage disorders. Copyright \u00a9 2003 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.468","type":"journal-article","created":{"date-parts":[[2004,1,7]],"date-time":"2004-01-07T08:00:46Z","timestamp":1073462446000},"page":"85-92","source":"Crossref","is-referenced-by-count":21,"title":["Partial correction of the \u03b1\u2010galactosidase A deficiency and reduction of glycolipid storage in Fabry mice using synthetic vectors"],"prefix":"10.1002","volume":"6","author":[{"given":"Malgorzata","family":"Przybylska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I\u2010Huan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongmei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin 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