{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:26:34Z","timestamp":1788888394727,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T00:00:00Z","timestamp":1692316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD000912\u201044"],"award-info":[{"award-number":["HD000912\u201044"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glycogen storage disease type\u2010Ia (GSD\u2010Ia), characterized by impaired blood glucose homeostasis, is caused by a deficiency in glucose\u20106\u2010phosphatase\u2010\u03b1 (G6Pase\u2010\u03b1 or G6PC). Using the <jats:italic>G6pc<\/jats:italic>\u2010R83C mouse model of GSD\u2010Ia, we explored a CRISPR\/Cas9\u2010based double\u2010strand DNA oligonucleotide (dsODN) insertional strategy that uses the nonhomologous end\u2010joining repair mechanism to correct the pathogenic p.R83C variant in <jats:italic>G6pc<\/jats:italic> exon\u20102. The strategy is based on the insertion of a short dsODN into <jats:italic>G6pc<\/jats:italic> exon\u20102 to disrupt the native exon and to introduce an additional splice acceptor site and the correcting sequence. When transcribed and spliced, the edited gene would generate a wild\u2010type mRNA encoding the native G6Pase\u2010\u03b1 protein. The editing reagents formulated in lipid nanoparticles (LNPs) were delivered to the liver. Mice were treated either with one dose of LNP\u2010dsODN at age 4\u2009weeks or with two doses of LNP\u2010dsODN at age 2 and 4\u2009weeks. The <jats:italic>G6pc<\/jats:italic>\u2010R83C mice receiving successful editing expressed ~4% of normal hepatic G6Pase\u2010\u03b1 activity, maintained glucose homeostasis, lacked hypoglycemic seizures, and displayed normalized blood metabolite profile. The outcomes are consistent with preclinical studies supporting previous gene augmentation therapy which is currently in clinical trials. This editing strategy may offer the basis for a therapeutic approach with an earlier clinical intervention than gene augmentation, with the additional benefit of a potentially permanent correction of the GSD\u2010Ia phenotype.<\/jats:p>","DOI":"10.1002\/jimd.12660","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T15:49:47Z","timestamp":1689781787000},"page":"1147-1158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>CRISPR\/Cas9<\/scp>\u2010based double\u2010strand oligonucleotide insertion strategy corrects metabolic abnormalities in murine glycogen storage disease type\u2010Ia"],"prefix":"10.1002","volume":"46","author":[{"given":"Ananya","family":"Samanta","sequence":"first","affiliation":[{"name":"Section on Cellular Differentiation, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes 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