Use of nonviral promoters in adenovirus‐mediated gene therapy: reduction of lysosomal storage in the aspartylglucosaminuria mouse

摘要: Background Aspartylglucosaminuria (AGU) is a lysosomal storage disease with severe neurodegenerative clinical features resulting from the deficiency of aspartylglucosaminidase (AGA). The AGU knockout mouse good model to test different therapy strategies, as it mimics well human pathogenesis exhibiting vacuoles in all tissues. In this study we investigated efficiency nonviral promoters adenovirus-mediated gene therapy. Methods The deficient corrective enzyme, AGA, was expressed using two tissue-specific promoters, neuron-specific enolase (NSE), astrocyte-specific (GFAP) and endogenous AGA promoter. An intrastriatal injection site chosen due its wide connections central nervous system (CNS). expression analyzed 1 week, 2 weeks, 4 months after virus by AGA-specific immunostaining. A correction brain treated mice also studied toluidine blue stained thin sections. Results The overexpressed enzyme detected addition site, ipsilateral parietal cortex indicating migration tissue. Duration markedly longer viruses used compared green fluorescent protein (GFP) driven viral cytomegalovirus (CMV) most animals decreased at least 50% untreated brains. Remarkably, >90% found NSE promoter weeks injection. Additionally, partial clearance demonstrated contralateral side brain. Conclusions These data implicate that are especially useful virus-mediated aiming long-term expression. Copyright © 2006 John Wiley & Sons, Ltd.