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Here, we demonstrated that adeno-associated virus\u2013mediated (AAV-mediated) systemic gene transfer reversed glycogen storage in all key therapeutic targets \u2014 skeletal and cardiac muscles, the diaphragm, and the central nervous system \u2014 in both young and severely affected old\n                    <jats:italic>Gaa<\/jats:italic>\n                    -knockout mice. Furthermore, the therapy reversed secondary cellular abnormalities in skeletal muscle, such as those in autophagy and mTORC1\/AMPK signaling. We used an AAV9 vector encoding a chimeric human GAA protein with enhanced uptake and secretion to facilitate efficient spread of the expressed protein among multiple target tissues. These results lay the groundwork for a future clinical development strategy in Pompe disease.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.170199","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T12:01:41Z","timestamp":1689681701000},"source":"Crossref","is-referenced-by-count":15,"title":["AAV-mediated delivery of secreted acid \u03b1-glucosidase with enhanced uptake corrects neuromuscular pathology in Pompe mice"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5450-5184","authenticated-orcid":true,"given":"Naresh K.","family":"Meena","sequence":"first","affiliation":[{"name":"Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, 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