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Interleukin\u201022 (IL\u201022), crucial for liver cell survival, shows potential in treating liver diseases by regulating repair and regeneration through signal transducer and activator of transcription 3 (STAT3) activation. However, the short half\u2010life and off\u2010target effects limit its clinical applications. To address these issues, lipid nanoparticles are employed to deliver synthetic IL\u201022 mRNA (IL\u201022\/NP) for in situ IL\u201022 expression in hepatocytes. The study reveals that IL\u201022\/NP exhibits liver\u2010targeted IL\u201022 expression, with increased IL\u201022 levels detected in the liver as early as 3\u00a0h postintravenous injection, lasting up to 96\u00a0h. Furthermore, IL\u201022\/NP activates STAT3\u00a0signaling in an autocrine or paracrine manner to upregulate downstream factors Bcl\u2010xL and CyclinD1, inhibiting hepatocyte apoptosis and promoting cell proliferation. The therapeutic efficacy of IL\u201022\/NP is demonstrated in both chronic and acute liver injury models, suggesting IL\u201022 mRNA delivery as a promising treatment strategy for hepatitis and liver diseases involving hepatocellular injury.<\/jats:p>","DOI":"10.1002\/smll.202401499","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T07:47:51Z","timestamp":1722412071000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Delivery of Synthetic Interleukin\u201022 mRNA to Hepatocytes via Lipid Nanoparticles Alleviates Liver Injury"],"prefix":"10.1002","volume":"20","author":[{"given":"Hanxiang","family":"Ouyang","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery the Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang 310009 China"},{"name":"Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary 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