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G6Pase-\u03b1 is critical for maintaining interprandial euglycemia. GSD1a patients exhibit life-threatening hypoglycemia and long-term liver complications including hepatocellular adenomas (HCAs) and carcinomas (HCCs). There is no treatment for GSD1a and the current standard-of-care for managing hypoglycemia (Glycosade<jats:sup>\u00ae<\/jats:sup>\/modified cornstarch) fails to prevent HCA\/HCC risk. Therapeutic modalities such as enzyme replacement therapy and gene therapy are not ideal options for patients due to challenges in drug-delivery, efficacy, and safety. To develop a new treatment for GSD1a capable of addressing both the life-threatening hypoglycemia and HCA\/HCC risk, we encapsulated engineered mRNAs encoding human G6Pase-\u03b1 in lipid nanoparticles. We demonstrate the efficacy and safety of our approach in a preclinical murine model that phenotypically resembles the human condition, thus presenting a potential therapy that could have a significant therapeutic impact on the treatment of GSD1a.<\/jats:p>","DOI":"10.1038\/s41467-021-23318-2","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T10:02:59Z","timestamp":1621936979000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage 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