{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:05:59Z","timestamp":1789020359520,"version":"build-2803163510"},"reference-count":133,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Med"],"abstract":"<jats:p>Type I glycogen storage diseases (GSD-I) consist of two major autosomal recessive disorders, GSD-Ia, caused by a reduction of glucose-6-phosphatase-\u03b1 (G6Pase-\u03b1 or G6PC) activity and GSD-Ib, caused by a reduction in the glucose-6-phosphate transporter (G6PT or SLC37A4) activity. The G6Pase-\u03b1 and G6PT are functionally co-dependent. Together, the G6Pase-\u03b1\/G6PT complex catalyzes the translocation of G6P from the cytoplasm into the endoplasmic reticulum lumen and its subsequent hydrolysis to glucose that is released into the blood to maintain euglycemia. Consequently, all GSD-I patients share a metabolic phenotype that includes a loss of glucose homeostasis and long-term risks of hepatocellular adenoma\/carcinoma and renal disease. A rigorous dietary therapy has enabled GSD-I patients to maintain a normalized metabolic phenotype, but adherence is challenging. Moreover, dietary therapies do not address the underlying pathological processes, and long-term complications still occur in metabolically compensated patients. Animal models of GSD-Ia and GSD-Ib have delineated the disease biology and pathophysiology, and guided development of effective gene therapy strategies for both disorders. Preclinical studies of GSD-I have established that recombinant adeno-associated virus vector-mediated gene therapy for GSD-Ia and GSD-Ib are safe, and efficacious. A phase III clinical trial of rAAV-mediated gene augmentation therapy for GSD-Ia (NCT05139316) is in progress as of 2023. A phase I clinical trial of mRNA augmentation for GSD-Ia was initiated in 2022 (NCT05095727). Alternative genetic technologies for GSD-I therapies, such as gene editing, are also being examined for their potential to improve further long-term outcomes.<\/jats:p>","DOI":"10.3389\/fmmed.2023.1167091","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T07:00:22Z","timestamp":1680246022000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Gene therapy and genome editing for type I glycogen storage diseases"],"prefix":"10.3389","volume":"3","author":[{"given":"Janice Y.","family":"Chou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Mansfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1086\/301727","article-title":"The gene for glycogen storage disease type 1b maps to chromosome 11q23","volume":"62","author":"Annabi","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1038\/s41587-020-0561-9","article-title":"Genome editing with CRISPR-Cas nucleases, base editors, transposases and prime editors","volume":"38","author":"Anzalone","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1602","DOI":"10.1016\/j.ymthe.2020.12.027","article-title":"Correction of metabolic abnormalities in a mouse model of glycogen storage disease type Ia by CRISPR\/Cas9-based gene editing","volume":"29","author":"Arnaoutova","year":"2021","journal-title":"Mol. Ther."},{"key":"B4","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1007\/s00424-003-1105-0","article-title":"The human sugar-phosphate\/phosphate exchanger family SLC37","volume":"447","author":"Bartoloni","year":"2004","journal-title":"Pflugers Arch."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.15252\/embj.201694699","article-title":"Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition","volume":"35","author":"Bazzini","year":"2016","journal-title":"EMBO J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1056\/NEJMoa0805051","article-title":"A syndrome with congenital neutropenia and mutations in G6PC3","volume":"360","author":"Boztug","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1177\/030098589503200502","article-title":"Glycogen storage disease type Ia in two littermate Maltese puppies","volume":"32","author":"Brix","year":"1995","journal-title":"Vet. Path"},{"key":"B8","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1007\/s10545-018-0223-y","article-title":"Long-term complications of glycogen storage disease type Ia in the canine model treated with gene replacement therapy","volume":"41","author":"Brooks","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"3090","DOI":"10.1038\/s41467-021-23318-2","article-title":"mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease","volume":"12","author":"Cao","year":"2021","journal-title":"Nat. Commun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/0958-1669(92)90082-t","article-title":"Adeno-associated virus vectors","volume":"3","author":"Carter","year":"1992","journal-title":"Curr. Opin. Biotechnol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"34280","DOI":"10.1074\/jbc.M006439200","article-title":"Structural requirements for the stability and microsomal transport activity of the human glucose-6-phosphate transporter","volume":"275","author":"Chen","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3199","DOI":"10.1093\/hmg\/11.25.3199","article-title":"Structure-function analysis of the glucose-6-phosphate transporter deficient in glycogen storage disease type Ib","volume":"11","author":"Chen","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2547","DOI":"10.1093\/hmg\/ddg263","article-title":"Impaired glucose homeostasis, neutrophil trafficking and function in mice lacking the glucose-6-phosphate transporter","volume":"12","author":"Chen","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2206","DOI":"10.1096\/fj.07-104851","article-title":"The Glucose-6-phosphate transporter is a phosphate-linked antiporter deficient in glycogen storage disease type Ib and Ic","volume":"22","author":"Chen","year":"2008","journal-title":"FASEB J."},{"key":"B15","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1056\/NEJM198401193100306","article-title":"Cornstarch therapy in type I glycogen storage disease","volume":"310","author":"Chen","year":"1984","journal-title":"N. Engl. J. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1172\/JCI30443","article-title":"Impaired neutrophil activity and increased susceptibility to bacterial infection in mice lacking glucose-6-phosphatase-beta","volume":"117","author":"Cheung","year":"2007","journal-title":"J. Clin. Invest."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e1006819","DOI":"10.1371\/journal.pgen.1006819","article-title":"Downregulation of SIRT1 signaling underlies hepatic autophagy impairment in glycogen storage disease type Ia","volume":"13","author":"Cho","year":"2017","journal-title":"PLoS Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1002\/jimd.12056","article-title":"Gene therapy prevents hepatic tumor initiation in murine glycogen storage disease type Ia at the tumor-developing stage","volume":"42","author":"Cho","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1016\/j.bbrc.2018.03.083","article-title":"Hepatic glucose-6-phosphatase-\u03b1 deficiency leads to metabolic reprogramming in glycogen storage disease type Ia","volume":"498","author":"Cho","year":"","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B20","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1007\/s10545-018-0192-1","article-title":"Sirtuin signaling controls mitochondrial function in glycogen storage disease type Ia","volume":"41","author":"Cho","year":"","journal-title":"J. Inherit. Metab. Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1007\/s10545-018-0180-5","article-title":"Molecular biology and gene therapy for glycogen storage disease type Ib","volume":"41","author":"Chou","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nrendo.2010.189","article-title":"Glycogen storage disease type I and G6Pase-\u03b2 deficiency: Etiology and therapy","volume":"6","author":"Chou","year":"","journal-title":"Nat. Rev. Endocrinol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1097\/MOH.0b013e328331df85","article-title":"Neutropenia in type Ib glycogen storage disease","volume":"17","author":"Chou","year":"","journal-title":"Curr. Opin. Hematol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1007\/s10545-014-9772-x","article-title":"Type I glycogen storage diseases: Disorders of the glucose-6-phosphatase\/glucose-6-phosphate transporter complexes","volume":"38","author":"Chou","year":"2015","journal-title":"J. Inherit. Metab. Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.livres.2017.12.001","article-title":"Recent development and gene therapy for glycogen storage disease type Ia","volume":"1","author":"Chou","year":"2017","journal-title":"Liver Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1002\/humu.20772","article-title":"Mutations in the glucose-6-phosphatase-\u03b1 (G6PC) gene that cause type Ia glycogen storage disease","volume":"29","author":"Chou","year":"2008","journal-title":"Hum. Mutat."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1517\/14712598.2011.578067","article-title":"Recombinant AAV-directed gene therapy for type I glycogen storage diseases","volume":"1","author":"Chou","year":"2011","journal-title":"Expert Opin. Biol. Ther."},{"key":"B28","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/B978-0-12-800223-0.00010-4","article-title":"The SLC37 family of sugar-phosphate\/phosphate exchangers","volume":"73","author":"Chou","year":"2014","journal-title":"Curr. Top. Membr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"121","DOI":"10.2174\/1566524024605798","article-title":"Type I glycogen storage diseases: Disorders of the glucose-6-phosphatase complex","volume":"2","author":"Chou","year":"2002","journal-title":"Curr. Mol. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.3945\/ajcn.2008.26352","article-title":"Use of modified cornstarch therapy to extend fasting in glycogen storage disease types Ia and Ib","volume":"88","author":"Correia","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1038\/mt.2008.72","article-title":"Gene delivery to the juvenile mouse liver using AAV2\/8 vectors","volume":"16","author":"Cunningham","year":"2008","journal-title":"Mol. Ther."},{"key":"B32","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/pedi.12540","article-title":"Prevention of complications in glycogen storage disease type Ia with optimization of metabolic control","volume":"18","author":"Dambska","year":"2017","journal-title":"Pediatr. Diabetes"},{"key":"B33","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/j.ymthe.2004.12.022","article-title":"Comparison of the ability of adeno-associated viral vectors pseudotyped with serotype 2, 5, and 8 capsid proteins to mediate efficient transduction of the liver in murine and nonhuman primate models","volume":"11","author":"Davidoff","year":"2005","journal-title":"Mol. Ther."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2101","DOI":"10.1089\/hum.1996.7.17-2101","article-title":"Quantitative analysis of the packaging capacity of recombinant adeno-associated virus","volume":"7","author":"Dong","year":"1996","journal-title":"Hum. Gene Ther."},{"key":"B35","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.jhep.2015.10.008","article-title":"Induction of autophagy improves hepatic lipid metabolism in glucose-6-phosphatase deficiency","volume":"64","author":"Farah","year":"2016","journal-title":"J. Hepatol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"3227","DOI":"10.1128\/JVI.70.5.3227-3234.1996","article-title":"Second-strand synthesis is a rate limiting step for efficient transduction by recombinant adeno-associated virus vectors","volume":"70","author":"Ferrari","year":"1996","journal-title":"J. Virol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/s41576-020-00298-5","article-title":"Gene therapy using haematopoietic stem and progenitor cells","volume":"22","author":"Ferrari","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"B38","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1128\/JVI.70.1.520-532.1996","article-title":"Transduction with recombinant adeno-associated virus for gene therapy is limited by leading-strand synthesis","volume":"70","author":"Fisher","year":"1996","journal-title":"J. Virol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1038\/s41431-021-00959-x","article-title":"The LOVD3 platform: Efficient genome-wide sharing of genetic variants","volume":"29","author":"Fokkema","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1038\/mt.2008.186","article-title":"Codon and mRNA sequence optimization of microdystrophin transgenes improves expression and physiological outcome in dystrophic mdx mice following AAV2\/8 gene transfer","volume":"16","author":"Foster","year":"2008","journal-title":"Mol. Ther."},{"key":"B41","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/nature24644","article-title":"Programmable base editing of A\u2022T to G\u2022C in genomic DNA without DNA cleavage","volume":"551","author":"Gaudelli","year":"2017","journal-title":"Nature"},{"key":"B42","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1093\/hmg\/ddac197","article-title":"Molecular mechanism underlying impaired hepatic autophagy in glycogen storage disease type Ib","volume":"32","author":"Gautam","year":"2023","journal-title":"Hum. Mol. Genet."},{"key":"B43","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/s0014-5793(97)01463-4","article-title":"Sequence of a putative glucose 6-phosphate translocase, mutated in glycogen storage disease type Ib","volume":"419","author":"Gerin","year":"1997","journal-title":"FEBS Lett."},{"key":"B44","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/sj.gt.3302650","article-title":"Long-term correction of murine glycogen storage disease type Ia by recombinant adeno-associated virus-1-mediated gene transfer","volume":"13","author":"Ghosh","year":"2006","journal-title":"Gene Ther."},{"key":"B45","doi-asserted-by":"publisher","first-page":"32837","DOI":"10.1074\/jbc.M201853200","article-title":"The catalytic center of glucose-6-phosphatase: His176 is the nucleophile forming the phosphohistidine-enzyme intermediate during catalysis","volume":"277","author":"Ghosh","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1016\/j.jhep.2018.07.017","article-title":"Dietary exacerbation of metabolic stress leads to accelerated hepatic carcinogenesis in glycogen storage disease type Ia","volume":"69","author":"Gjorgjieva","year":"2018","journal-title":"J. Hepatol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1056\/NEJM197602192940805","article-title":"Continuous nocturnal intragastric feeding for management of type 1 glycogen-storage disease","volume":"294","author":"Greene","year":"1976","journal-title":"N. Engl. J. Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1089\/hum.2015.025","article-title":"Adeno-associated virus at 50: A golden anniversary of discovery, research, and gene therapy success\u2013a personal perspective","volume":"26","author":"Hastie","year":"2015","journal-title":"Hum. Gene Ther."},{"key":"B49","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.cels.2022.05.001","article-title":"Diploid hepatocytes drive physiological liver renewal in adult humans","volume":"13","author":"Heinke","year":"2022","journal-title":"Cell. Syst."},{"key":"B50","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1089\/104454901316976073","article-title":"Glucocorticoids activate transcription of the gene for the glucose-6-phosphate transporter, deficient in glycogen storage disease type 1b","volume":"20","author":"Hiraiwa","year":"2001","journal-title":"DNA Cell. Biol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"5532","DOI":"10.1074\/jbc.274.9.5532","article-title":"Inactivation of the glucose-6-phosphate transporter causes glycogen storage disease type 1b","volume":"274","author":"Hiraiwa","year":"1999","journal-title":"J. Biol. Chem."},{"key":"B52","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.coviro.2014.05.007","article-title":"Parvovirus glycan interactions","volume":"7","author":"Huang","year":"2014","journal-title":"Curr. Opin. Virol."},{"key":"B133","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1089\/hum.2019.102","article-title":"Challenges of gene therapy for the treatment of glycogen storage diseases type I and type III","volume":"30","author":"Jauze","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1177\/38.10.2169492","article-title":"Quantitative histochemical analysis of glucose-6-phosphatase activity in rat liver using an optimized cerium-diaminobenzidine method","volume":"38","author":"Jonges","year":"1990","journal-title":"J. Histochem. Cytochem"},{"key":"B54","doi-asserted-by":"publisher","first-page":"5115","DOI":"10.1093\/hmg\/ddv230","article-title":"Mice expressing reduced levels of hepatic glucose-6-phosphatase-\u03b1 activity do not develop age-related insulin resistance or obesity","volume":"24","author":"Kim","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.1093\/hmg\/ddx097","article-title":"Downregulation of pathways implicated in liver inflammation and tumorigenesis of glycogen storage disease type Ia mice receiving gene therapy","volume":"26","author":"Kim","year":"","journal-title":"Hum. Mol. Genet."},{"key":"B56","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.ymgme.2017.01.003","article-title":"Glycogen storage disease type Ia mice with less than 2% of normal hepatic glucose-6-phosphatase-\u03b1 activity restored are at risk of developing hepatic tumors","volume":"120","author":"Kim","year":"","journal-title":"Mol. Genet. Metab."},{"key":"B57","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1038\/gim.2014.128","article-title":"Diagnosis and management of glycogen storage disease type I: A practice guideline of the American College of medical genetics and genomics","volume":"16","author":"Kishnani","year":"2014","journal-title":"Genet. Med."},{"key":"B58","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1354\/vp.38-1-83","article-title":"Canine model and genomic structural organization of glycogen storage disease type Ia (GSD Ia)","volume":"38","author":"Kishnani","year":"2001","journal-title":"Vet. Pathol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/mt.2008.15","article-title":"AAV vector-mediated reversal of hypoglycemia in canine and murine glycogen storage disease type Ia","volume":"16","author":"Koeberl","year":"2008","journal-title":"Ther"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1038\/sj.gt.3302774","article-title":"Early, sustained efficacy of adeno-associated virus vector-mediated gene therapy in glycogen storage disease type Ia","volume":"13","author":"Koeberl","year":"2006","journal-title":"Gene Ther."},{"key":"B61","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/nature17946","article-title":"Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage","volume":"533","author":"Komor","year":"2016","journal-title":"Nature"},{"key":"B62","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s11095-007-9431-0","article-title":"Designer gene delivery vectors: Molecular engineering and evolution of adeno-associated viral vectors for enhanced gene transfer","volume":"25","author":"Kwon","year":"2008","journal-title":"Pharm. Res."},{"key":"B63","doi-asserted-by":"publisher","first-page":"4395","DOI":"10.1093\/hmg\/ddx325","article-title":"Liver-directed gene therapy for murine glycogen storage disease type Ib","volume":"26","author":"Kwon","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"B64","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1007\/s10545-018-0199-7","article-title":"Long-term safety and efficacy of AAV gene therapy in the canine model of glycogen storage disease type Ia","volume":"41","author":"Lee","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1002\/hep.25717","article-title":"Prevention of hepatocellular adenoma and correction of metabolic abnormalities in murine glycogen storage disease type Ia by gene therapy","volume":"56","author":"Lee","year":"2012","journal-title":"Hepatology"},{"key":"B66","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.ymgmr.2015.03.001","article-title":"Minimal hepatic glucose-6-phosphatase-\u03b1 activity required to sustain survival and prevent hepatocellular adenoma formation in murine glycogen storage disease type Ia","volume":"3","author":"Lee","year":"2015","journal-title":"Mol. Genet. Metab. Reposts"},{"key":"B67","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.ymgme.2013.06.014","article-title":"The Upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia","volume":"110","author":"Lee","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"B68","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/ng0696-203","article-title":"Glucose-6-phosphatase dependent substrate transport in the glycogen storage disease type 1a mouse","volume":"13","author":"Lei","year":"1996","journal-title":"Nat. Genet."},{"key":"B69","first-page":"766","article-title":"Genetic basis of glycogen storage disease type 1a: Prevalent mutations at the glucose-6-phosphatase locus","volume":"57","author":"Lei","year":"","journal-title":"Am. J. Hum. Genet."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1994","DOI":"10.1172\/JCI117192","article-title":"Identification of mutations in the gene for glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1a","volume":"93","author":"Lei","year":"1994","journal-title":"J. Clin. Invest."},{"key":"B71","doi-asserted-by":"publisher","first-page":"11882","DOI":"10.1074\/jbc.270.20.11882","article-title":"Structure-function analysis of human glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1a","volume":"270","author":"Lei","year":"","journal-title":"J. Biol. Chem."},{"key":"B72","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1126\/science.8211187","article-title":"Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease type 1a","volume":"262","author":"Lei","year":"1993","journal-title":"Science"},{"key":"B73","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/s41576-019-0205-4","article-title":"Engineering adeno-associated virus vectors for gene therapy","volume":"21","author":"Li","year":"2020","journal-title":"Nat. Rev. Genet."},{"key":"B74","doi-asserted-by":"publisher","first-page":"31656","DOI":"10.1074\/jbc.273.48.31656","article-title":"Cloning and characterization of cDNAs encoding a candidate glycogen storage disease type 1b protein in rodents","volume":"273","author":"Lin","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B75","doi-asserted-by":"publisher","first-page":"14096","DOI":"10.1021\/bi9703249","article-title":"The role of HNF1alpha, HNF3gamma, and cyclic AMP in glucose-6-phosphatase gene activation","volume":"36","author":"Lin","year":"1997","journal-title":"Biochemistry"},{"key":"B76","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1080\/10717544.2018.1474964","article-title":"Delivering CRISPR: A review of the challenges and approaches","volume":"25","author":"Lino","year":"2018","journal-title":"Drug Deliv."},{"key":"B77","doi-asserted-by":"publisher","first-page":"5559","DOI":"10.1016\/j.cell.2021.10.001","article-title":"Glycogen accumulation and phase separation drives liver tumor initiation","volume":"184","author":"Liu","year":"2021","journal-title":"Cell."},{"key":"B78","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.molmed.2014.09.003","article-title":"A critical analysis of codon optimization in human therapeutics","volume":"20","author":"Mauro","year":"2014","journal-title":"Trends Mol. Med."},{"key":"B79","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/mt.2010.250","article-title":"The complex and evolving story of T cell activation to AAV vector-encoded transgene products","volume":"19","author":"Mays","year":"2011","journal-title":"Mol. Ther."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1038\/sj.gt.3301514","article-title":"Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis","volume":"8","author":"Mccarty","year":"2001","journal-title":"Gene Ther."},{"key":"B81","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.ymthe.2020.12.007","article-title":"Current clinical applications of in vivo Gene therapy with AAVs","volume":"29","author":"Mendell","year":"2021","journal-title":"Mol. Ther."},{"key":"B82","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0065-2660(09)67002-4","article-title":"Adeno-associated viral vectors and their redirection to cell-type specific receptors","volume":"67","author":"Michelfelder","year":"2009","journal-title":"Adv. Genet."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/j.tibtech.2019.03.008","article-title":"CRISPR\/Cas-mediated base editing: Technical considerations and practical applications","volume":"37","author":"Molla","year":"2019","journal-title":"Trends Biotechnol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"e143780","DOI":"10.1172\/JCI143780","article-title":"Overcoming innate immune barriers that impede AAV gene therapy vectors","volume":"131","author":"Muhuri","year":"2021","journal-title":"J. Clin. Invest."},{"key":"B85","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.jhep.2010.08.014","article-title":"Targeted deletion of liver glucose-6 phosphatase mimics glycogen storage disease type 1a including development of multiple adenomas","volume":"54","author":"Mutel","year":"2011","journal-title":"J. Hepatol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/j.tibtech.2018.03.004","article-title":"Strategies for in vivo genome editing in nondividing cells","volume":"36","author":"Nami","year":"2018","journal-title":"Trends Biotechnol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1089\/hum.2022.169","article-title":"Liver gene therapy","volume":"33","author":"Nathwani","year":"2022","journal-title":"Hum. Gene Ther."},{"key":"B88","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1111\/bjh.17155","article-title":"Haemophilia, the journey in search of a cure. 1960\u20132020","volume":"191","author":"Nathwani","year":"2020","journal-title":"Br. J. Haematol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"3107","DOI":"10.1016\/j.ymthe.2021.09.002","article-title":"In vivo somatic cell base editing and prime editing","volume":"29","author":"Newby","year":"2021","journal-title":"Mol. Ther."},{"key":"B90","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1007\/s10545-017-0054-2","article-title":"Tight metabolic control plus ACE inhibitor therapy improves GSD I nephropathy","volume":"40","author":"Okechuku","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"key":"B91","doi-asserted-by":"publisher","first-page":"e23157","DOI":"10.1371\/journal.pone.0023157","article-title":"SLC37A1 and SLC37A2 are phosphate-linked, glucose-6-phosphate antiporters","volume":"6","author":"Pan","year":"2011","journal-title":"PLoS One"},{"key":"B92","doi-asserted-by":"publisher","first-page":"6144","DOI":"10.1074\/jbc.273.11.6144","article-title":"Transmembrane topology of glucose-6-phosphatase","volume":"273","author":"Pan","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B93","doi-asserted-by":"publisher","first-page":"13865","DOI":"10.1074\/jbc.274.20.13865","article-title":"Transmembrane topology of human Glucose-6-phosphate transporter","volume":"274","author":"Pan","year":"1999","journal-title":"J. Biol. Chem."},{"key":"B94","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1136\/gutjnl-2016-313565","article-title":"CRISPR\/Cas9: At the cutting edge of hepatology","volume":"66","author":"Pankowicz","year":"2017","journal-title":"Gut"},{"key":"B95","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1002\/hep.32408","article-title":"Liver zonation, revisited","volume":"76","author":"Paris","year":"2022","journal-title":"Hepatology"},{"key":"B96","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1002\/dvg.20538","article-title":"Generation of mice with a conditional allele for G6pc","volume":"47","author":"Peng","year":"2009","journal-title":"Genesis"},{"key":"B97","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1080\/14712598.2020.1817375","article-title":"Liver-directed gene-based therapies for inborn errors of metabolism","volume":"21","author":"Piccolo","year":"2021","journal-title":"Expert Opin. Biol. Ther."},{"key":"B98","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/s41573-020-0084-6","article-title":"Base editing: Advances and therapeutic opportunities","volume":"19","author":"Porto","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"B99","first-page":"49","article-title":"Viral expression cassette elements to enhance transgene target specificity and expression in gene therapy","volume":"19","author":"Powell","year":"2015","journal-title":"Discov. Med."},{"key":"B100","doi-asserted-by":"publisher","first-page":"E751","DOI":"10.1152\/ajpendo.00745.2009","article-title":"AMPK and SIRT1: A long-standing partnership?","volume":"298","author":"Ruderman","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B101","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1007\/s10545-018-0211-2","article-title":"Development and characterization of an inducible mouse model for glycogen storage disease type Ib","volume":"41","author":"Raggi","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"B102","doi-asserted-by":"publisher","first-page":"S20","DOI":"10.1007\/s00431-002-0999-4","article-title":"Glycogen storage disease type I: Diagnosis, management, clinical course and outcome. Results of the European study on glycogen storage disease type I (ESGSD I)","volume":"161","author":"Rake","year":"2002","journal-title":"Eur. J. Pediatr."},{"key":"B103","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1016\/j.cell.2013.08.021","article-title":"Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity","volume":"154","author":"Ran","year":"2013","journal-title":"Cell."},{"key":"B104","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/s41586-018-0243-7","article-title":"Codon-specific translation reprogramming promotes resistance to targeted therapy","volume":"558","author":"Rapino","year":"2018","journal-title":"Nature"},{"key":"B105","first-page":"564","article-title":"Sustained efficacy and safety at week 52 and up to three years in adults with glycogen storage disease type Ia (GSDIa): Results from a phase 1\/2 clinical trial of DTX401, an AAV8-mediated, liver-directed gene therapy","volume-title":"Mol. Ther.","author":"Riba-Wolman","year":"2022"},{"key":"B106","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1080\/14712598.2021.1865303","article-title":"Adeno-associated virus (AAV) capsid engineering in liver-directed gene therapy","volume":"21","author":"Rodr\u00edguez-M\u00e1rquez","year":"2021","journal-title":"Expert Opin. Biol. Ther."},{"key":"B107","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1016\/j.ymthe.2018.01.006","article-title":"G6PC mRNA therapy positively regulates fasting blood glucose and decreases liver abnormalities in a mouse model of glycogen storage disease 1a","volume":"26","author":"Roseman","year":"2018","journal-title":"Mol. Ther."},{"key":"B108","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1093\/advances\/nmz092","article-title":"Dietary management of the glycogen storage diseases: Evolution of treatment and ongoing controversies","volume":"11","author":"Ross","year":"2020","journal-title":"Adv. Nutr."},{"key":"B109","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1038\/nbt.4148","article-title":"Adenine base editing in mouse embryos and an adult mouse model of Duchenne muscular dystrophy","volume":"36","author":"Ryu","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"B110","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12916-017-0798-4","article-title":"Genome editing for inborn errors of metabolism: Advancing towards the clinic","volume":"15","author":"Schneller","year":"2017","journal-title":"BMC Med."},{"key":"B111","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/gene.20039","article-title":"Efficient temporally controlled targeted somatic mutagenesis in hepatocytes of the mouse","volume":"39","author":"Schuler","year":"2004","journal-title":"Genesis"},{"key":"B112","doi-asserted-by":"publisher","first-page":"47098","DOI":"10.1074\/jbc.M309472200","article-title":"A glucose-6-phosphate hydrolase, widely expressed outside the liver, can explain age-dependent resolution of hypoglycemia in glycogen storage disease type Ia","volume":"278","author":"Shieh","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B113","doi-asserted-by":"publisher","first-page":"5047","DOI":"10.1074\/jbc.M110486200","article-title":"The molecular basis of glycogen storage disease type 1a: Structure and function analysis of mutations in glucose-6-phosphatase","volume":"277","author":"Shieh","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B114","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1126\/science.1243490","article-title":"Exonic transcription factor binding directs codon choice and affects protein evolution","volume":"342","author":"Stergachis","year":"2013","journal-title":"Science"},{"key":"B115","doi-asserted-by":"publisher","first-page":"3110","DOI":"10.1128\/jvi.78.6.3110-3122.2004","article-title":"Rapid uncoating of vector genomes is the key to efficient liver transduction with pseudotyped adeno-associated virus vectors","volume":"78","author":"Thomas","year":"2004","journal-title":"J. Virol."},{"key":"B116","unstructured":"A study of adeno-associated virus serotype 8-mediated gene transfer of glucose-6-phosphatase in patients with glycogen storage disease type Ia (GSDIa)"},{"key":"B117","unstructured":"Safety and dose-finding study of DTX401 (AAV8G6PC) in adults with glycogen storage disease type Ia (GSDIa)"},{"key":"B118","unstructured":"Ultragenyx corporate presentation, november 2022, slide 33"},{"key":"B119","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.ymthe.2019.12.010","article-title":"AAV vector immunogenicity in humans: A long journey to successful gene transfer","volume":"28","author":"Verdera","year":"2020","journal-title":"Mol. Ther."},{"key":"B120","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1067\/mpd.2000.105232","article-title":"Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib: Results of the European study on glycogen storage disease type I","volume":"137","author":"Visser","year":"2000","journal-title":"J. Pediatr."},{"key":"B121","doi-asserted-by":"publisher","first-page":"S83","DOI":"10.1007\/s00431-002-1010-0","article-title":"Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European Study on Glycogen Storage Disease Type 1","volume":"161","author":"Visser","year":"2002","journal-title":"Eur. J. Pediatr."},{"key":"B122","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","article-title":"Adeno-associated virus vector as a platform for gene therapy delivery","volume":"18","author":"Wang","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"B123","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1038\/sj.gt.3302133","article-title":"Rapid and highly efficient transduction by double-stranded adeno-associated virus vectors in vitro and in vivo","volume":"10","author":"Wang","year":"2003","journal-title":"Gene Ther."},{"key":"B124","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1182\/blood-2010-05-282707","article-title":"Codon optimization of human factor VIII cDNAs leads to high-level expression","volume":"117","author":"Ward","year":"2011","journal-title":"Blood"},{"key":"B125","doi-asserted-by":"publisher","first-page":"658399","DOI":"10.3389\/fimmu.2021.658399","article-title":"Anti-AAV antibodies in AAV gene therapy: Current challenges and possible solutions","volume":"12","author":"Weber","year":"2021","journal-title":"Front. Immunol."},{"key":"B126","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1089\/hum.2009.157","article-title":"Adeno-associated virus-mediated correction of a canine model of glycogen storage disease type Ia","volume":"21","author":"Weinstein","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"B127","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.ymthe.2006.05.009","article-title":"Adeno-associated virus serotypes: Vector toolkit for human gene therapy","volume":"14","author":"Wu","year":"2006","journal-title":"Mol. Ther."},{"key":"B128","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1038\/nbt.3469","article-title":"A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice","volume":"34","author":"Yang","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"B129","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1038\/mt.2010.64","article-title":"Complete normalization of hepatic G6PC deficiency in murine glycogen storage disease type Ia using gene therapy","volume":"18","author":"Yiu","year":"2010","journal-title":"Mol. Ther."},{"key":"B130","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1016\/j.jhep.2008.11.026","article-title":"Normoglycemia alone is insufficient to prevent long term complications of hepatocellular adenoma in glycogen storage disease type Ib mice","volume":"51","author":"Yiu","year":"2009","journal-title":"J. Hepatol."},{"key":"B131","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1002\/jimd.12069","article-title":"An evolutionary approach to optimizing glucose-6-phosphatase-\u03b1 enzymatic activity for gene therapy of glycogen storage disease type Ia","volume":"42","author":"Zhang","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"B132","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.bbrc.2020.04.124","article-title":"Gene therapy using a novel G6PC-S298C variant enhances the long-term efficacy for treating glycogen storage disease type Ia","volume":"527","author":"Zhang","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Frontiers in Molecular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmmed.2023.1167091\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T07:00:32Z","timestamp":1680246032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmmed.2023.1167091\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,31]]},"references-count":133,"alternative-id":["10.3389\/fmmed.2023.1167091"],"URL":"https:\/\/doi.org\/10.3389\/fmmed.2023.1167091","relation":{},"ISSN":["2674-0095"],"issn-type":[{"value":"2674-0095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,31]]},"article-number":"1167091"}}