{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:00:38Z","timestamp":1791165638802,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,4,4]],"date-time":"2007-04-04T00:00:00Z","timestamp":1175644800000},"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":[[2007,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The <jats:italic>Sleeping Beauty<\/jats:italic> (SB) transposon system is a non\u2010viral vector system that can integrate precise sequences into chromosomes. We evaluated the SB transposon system as a tool for gene therapy of mucopolysaccharidosis (MPS) types I and VII.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We constructed SB transposon plasmids for high\u2010level expression of human \u03b2\u2010glucuronidase (hGUSB) or \u03b1\u2010<jats:sc>L<\/jats:sc>\u2010iduronidase (hIDUA). Plasmids were delivered with and without SB transposase to mouse liver by rapid, high\u2010volume tail\u2010vein injection. We studied the duration of expressed therapeutic enzyme activity, transgene presence by PCR, lysosomal pathology by toluidine blue staining and cell\u2010mediated immune response histologically and by immunohistochemical staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Transgene frequency, distribution of transgene and enzyme expression in liver and the level of transgenic enzyme required for amelioration of lysosomal pathology were estimated in MPS I and VII mice. Without immunomodulation, initial GUSB and IDUA activities in plasma reached &gt; 100\u2010fold of wild\u2010type (WT) levels but fell to background within 4 weeks post\u2010injection. In immunomodulated transposon\u2010treated MPS I mice plasma IDUA persisted for over 3 months at up to 100\u2010fold WT activity in one\u2010third of MPS I mice, which was sufficient to reverse lysosomal pathology in the liver and, partially, in distant organs. Histological and immunohistochemical examination of liver sections in IDUA transposon\u2010treated WT mice revealed inflammation 10 days post\u2010injection consisting predominantly of mononuclear cells, some of which were CD4\u2010 or CD8\u2010positive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results demonstrate the feasibility of achieving prolonged expression of lysosomal enzymes in the liver and reversing MPS disease in adult mice with a single dose of therapeutic SB transposons. 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