{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:38:09Z","timestamp":1789616289617,"version":"build-2803163510"},"reference-count":50,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"15","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,4,11]]},"abstract":"<jats:p>\n            Primary hyperoxaluria type 1 (PH1) is a rare inherited liver disorder caused by alanine glyoxylate aminotransferase (AGT) dysfunction, leading to accumulation of glyoxylate which is then converted into oxalate. Excessive oxalate results in kidney damage due to deposition of oxalate crystals. We have developed an mRNA-based protein replacement therapy for PH1 to restore normal glyoxylate to glycine metabolism. Sequence optimized human\n            <jats:italic>AGT<\/jats:italic>\n            mRNA (\n            <jats:italic>hAGT<\/jats:italic>\n            mRNA) was encapsulated in lipopolyplex (LPP) and produced functional AGT enzyme in peroxisomes. Pharmacokinetics and pharmacodynamics (PK\/PD) were evaluated in vitro and in vivo. PK demonstrated that\n            <jats:italic>AGT<\/jats:italic>\n            mRNA and AGT protein maintained high expression levels for up to 48 hours. A single 2 mg\/kg dose in\n            <jats:italic>Agxt<\/jats:italic>\n            Q84\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            rats achieved a 70% reduction in urinary oxalate. Toxicological assessment identified the highest nonserious toxic dose (HNSTD) as 2 mg\/kg. These findings affirm the efficacy and safety of\n            <jats:italic>hAGT<\/jats:italic>\n            mRNA\/LPP and support its clinical application in PH1 treatment.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adt9694","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T17:58:41Z","timestamp":1744221521000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":13,"title":["Preclinical evaluation of AGT mRNA replacement therapy for primary hyperoxaluria type I disease"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6767-5027","authenticated-orcid":true,"given":"Taihua","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, 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Research of the Ministry of Education, China-Japan Union Hospital of Jilin University, Jilin University, Changchun 130062, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1146-7848","authenticated-orcid":true,"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9728-5430","authenticated-orcid":true,"given":"Haifa","family":"Shen","sequence":"additional","affiliation":[{"name":"Stemirna Therapeutics, Shanghai 201203, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8852-4501","authenticated-orcid":true,"given":"Hangwen","family":"Li","sequence":"additional","affiliation":[{"name":"Stemirna Therapeutics, Shanghai 201203, 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