{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T20:43:05Z","timestamp":1785357785612,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T00:00:00Z","timestamp":1586476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010275","name":"Deutsche Gesellschaft f\u00fcr Muskelkranke e.V.","doi-asserted-by":"publisher","award":["LiS1"],"award-info":[{"award-number":["LiS1"]}],"id":[{"id":"10.13039\/501100010275","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pompe disease is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of lysosomal acid alpha-glucosidase (GAA). The result of the GAA deficiency is a ubiquitous lysosomal and non-lysosomal accumulation of glycogen. The most affected tissues are heart, skeletal muscle, liver, and the nervous system. Replacement therapy with the currently approved enzyme relies on M6P-mediated endocytosis. However, therapeutic outcomes still leave room for improvement, especially with regard to skeletal muscles. We tested the uptake, activity, and effect on glucose metabolism of a non-phosphorylated recombinant human GAA produced in moss (moss-GAA). Three variants of moss-GAA differing in glycosylation pattern have been analyzed: two with terminal mannose residues in a paucimannosidic (Man3) or high-mannose (Man 5) configuration and one with terminal N-acetylglucosamine residues (GnGn). Compared to alglucosidase alfa the moss-GAA GnGn variant showed increased uptake in differentiated myotubes. Moreover, incubation of immortalized muscle cells of Gaa\u2212\/\u2212 mice with moss-GAA GnGn led to similarly efficient clearance of accumulated glycogen as with alglucosidase alfa. These initial data suggest that M6P-residues might not always be necessary for the cellular uptake in enzyme replacement therapy (ERT) and indicate the potential of moss-GAA GnGn as novel alternative drug for targeting skeletal muscle in Pompe patients.<\/jats:p>","DOI":"10.3390\/ijms21072642","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T04:45:31Z","timestamp":1586753131000},"page":"2642","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Moss-Derived Human Recombinant GAA Provides an Optimized Enzyme Uptake in Differentiated Human Muscle Cells of Pompe Disease"],"prefix":"10.3390","volume":"21","author":[{"given":"Stefan","family":"Hintze","sequence":"first","affiliation":[{"name":"Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Limmer","sequence":"additional","affiliation":[{"name":"Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Dabrowska-Schlepp","sequence":"additional","affiliation":[{"name":"Greenovation Biotech GmbH, 79108 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Berg","sequence":"additional","affiliation":[{"name":"Greenovation Biotech GmbH, 79108 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Krieghoff","sequence":"additional","affiliation":[{"name":"Greenovation Biotech GmbH, 79108 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Busch","sequence":"additional","affiliation":[{"name":"Greenovation Biotech GmbH, 79108 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schaaf","sequence":"additional","affiliation":[{"name":"Greenovation Biotech GmbH, 79108 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Meinke","sequence":"additional","affiliation":[{"name":"Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2757-8131","authenticated-orcid":false,"given":"Benedikt","family":"Schoser","sequence":"additional","affiliation":[{"name":"Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,10]]},"reference":[{"key":"ref_1","first-page":"440","article-title":"Identification of the base-pair substitution responsible for a human acid alpha glucosidase allele with lower \u201caffinity\u201d for glycogen (GAA 2) and transient gene expression in deficient cells","volume":"47","author":"Martiniuk","year":"1990","journal-title":"Am. 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