{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:28:18Z","timestamp":1781105298066,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1993,3,15]]},"abstract":"<jats:p>We have combined a receptor-mediated DNA delivery system with the endosomal lysis ability of adenovirus and shown that DNA can be delivered into primary hepatocytes, resulting in a high level of gene expression. When asialoorosomucoid conjugated with poly(L-lysine) was used to deliver the Escherichia coli beta-galactosidase gene into primary hepatocytes through binding with the hepatic asialoglycoprotein receptor, only a low level of beta-galactosidase was detectable, with less than 0.1% of the hepatocytes being transfected. This level of activity can be greatly enhanced by the cointernalization of the DNA.protein complex with a replication-defective adenovirus, resulting in 100% of the hepatocytes staining blue with 5-bromo-4-chloro-3-indolyl beta-D-galactoside. Quantitative analysis of beta-galactosidase expression also showed a 1000-fold enhancement of activity. To test the applicability of this DNA delivery system for the correction of phenylketonuria, a metabolic disorder that causes severe mental retardation in children, we have delivered the human phenylalanine hydroxylase (PAH) gene to hepatocytes derived from a PAH-deficient mouse strain and demonstrated complete reconstitution of enzymatic activity. This method shows great promise for efficient gene delivery to the liver for correction of hepatic disorders.<\/jats:p>","DOI":"10.1073\/pnas.90.6.2122","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:41:16Z","timestamp":1149064876000},"page":"2122-2126","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":118,"title":["Hepatic gene therapy: adenovirus enhancement of receptor-mediated gene delivery and expression in primary hepatocytes."],"prefix":"10.1073","volume":"90","author":[{"given":"R J","family":"Cristiano","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L C","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S L","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1993,3,15]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.90.6.2122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:34:16Z","timestamp":1649856856000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.90.6.2122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,3,15]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1993,3,15]]}},"alternative-id":["10.1073\/pnas.90.6.2122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.90.6.2122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,3,15]]},"assertion":[{"value":"1993-03-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}