Gene therapy with bilirubin-UDP-glucuronosyltransferase in the Gunn rat model of Crigler-Najjar syndrome type 1

Human Gene Therapy
Q LiB A French

Abstract

Crigler-Najjar syndrome type 1 (CN type 1) is an autosomal recessive disorder characterized by nonhemolytic jaundice resulting from mutations to the gene encoding bilirubin-UDP-glucuronosyltransferase (UDPGT). The Gunn rat is an accurate animal model of this disease because the bilirubin-UDPGT gene in this strain carries a premature stop codon. The primary objective of this study was to complement this deficiency in vivo using liver-directed gene therapy. The efficiency of adenovirus type 5 (Ad5)-mediated gene transfer to the neonatal rat liver was first assessed by intravenous (i.v.) injection of an Ad5 vector carrying a nuclear-localized LacZ gene. An Ad5 vector expressing the cDNA encoding human bilirubin-UDPGT (Ad5/CMV/hUG-Br1) was then generated and injected i.v. into neonatal Gunn rats. Plasma samples were collected and bilirubin levels were determined at regular intervals. Although the mean level of bilirubin in homozygous Gunn rats 1-2 days after birth was already 14.5-fold higher than that of heterozygous siblings, treatment with Ad5/CMV/hUG-Br1 reduced plasma bilirubin to normal levels within 1 week. Plasma bilirubin in the treated homozygous rats remained normal for 4 weeks before gradually climbing to intermediate l...Continue Reading

References

Aug 1, 1992·Nature Genetics·H A JaffeM Perricaudet
Aug 1, 1992·The Journal of Clinical Investigation·L D Stratford-PerricaudetP Briand
Mar 1, 1987·The Biochemical Journal·M R JacksonB Burchell
Sep 1, 1969·Clinica Chimica Acta; International Journal of Clinical Chemistry·S Winsten, B Cehelyk
Jan 1, 1995·Journal of Viral Hepatitis·W C NgL Lesmana
Jan 1, 1995·Progress in Nucleic Acid Research and Molecular Biology·I S Owens, J K Ritter
Feb 1, 1995·Journal of Virology·A L Kirchmaier, B Sugden
Jan 1, 1994·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·B Lichtiger
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·A J BettF L Graham
Sep 1, 1993·Cell Transplantation·S E Raper, J M Wilson
Nov 1, 1993·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·C H Brierley, B Burchell
Mar 1, 1996·Nature Genetics·J M Wilson
Apr 2, 1996·Proceedings of the National Academy of Sciences of the United States of America·J WalterK A High
Aug 1, 1996·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·C N van der VeereP L Jansen
Apr 1, 1956·Proceedings of the Society for Experimental Biology and Medicine·F WROBLEWSKI, J S LADUE
May 1, 1959·A.M.A. Journal of Diseases of Children·L JOHNSONR DAY

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Citations

Mar 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Gabriele ToiettaBrendan Lee
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·B T KrenC J Steer
Oct 7, 2006·Current Opinion in Gastroenterology·M L Schilsky
Nov 29, 2013·Gene Therapy·P S Montenegro-MirandaP J Bosma
Jun 12, 2012·Expert Opinion on Biological Therapy·Mario Di MatteoThierry Vandendriessche
Sep 6, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tuan Huy NguyenNicolas Ferry
Jul 16, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Zhen Jia, István Dankó
Feb 28, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiao-Kang LiTorayuki Okuyama
Dec 13, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Pascal van der WegenBob J Scholte
Apr 18, 2008·World Journal of Gastroenterology : WJG·Xi JinYou-Ming Li
Oct 1, 2007·Expert Review of Gastroenterology & Hepatology·Tuan Huy Nguyen, Nicolas Ferry
Mar 12, 2017·Molecular Pharmacology·Mei-Fei YuehRobert H Tukey
Jun 10, 2006·The Journal of Pharmacology and Experimental Therapeutics·Kristini K MilesJoseph K Ritter
Nov 1, 2008·Expert Review of Endocrinology & Metabolism·Emer FitzpatrickAnil Dhawan

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