{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:08:18Z","timestamp":1790629698999,"version":"4.1.0"},"reference-count":35,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"692","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,4,19]]},"abstract":"<jats:p>\n            Glutaric aciduria type I (GA-1) is an inborn error of metabolism with a severe neurological phenotype caused by the deficiency of glutaryl\u2013coenzyme A dehydrogenase (GCDH), the last enzyme of lysine catabolism. Current literature suggests that toxic catabolites in the brain are produced locally and do not cross the blood-brain barrier. In a series of experiments using knockout mice of the lysine catabolic pathway and liver cell transplantation, we uncovered that toxic GA-1 catabolites in the brain originated from the liver. Moreover, the characteristic brain and lethal phenotype of the GA-1 mouse model was rescued by two different liver-directed gene therapy approaches: Using an adeno-associated virus, we replaced the defective\n            <jats:italic>Gcdh<\/jats:italic>\n            gene or we prevented flux through the lysine degradation pathway by CRISPR deletion of the aminoadipate-semialdehyde synthase (\n            <jats:italic>Aass<\/jats:italic>\n            ) gene. Our findings question the current pathophysiological understanding of GA-1 and reveal a targeted therapy for this devastating disorder.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adf4086","type":"journal-article","created":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T17:58:18Z","timestamp":1681927098000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":27,"title":["Rescue of glutaric aciduria type I in mice by liver-directed therapies"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3428-2782","authenticated-orcid":true,"given":"Mercedes","family":"Barzi","sequence":"first","affiliation":[{"name":"Y.T. and Alice Chen Center for Genetics and Genomics, Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin 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