Life-Long Correction of Hyperbilirubinemia with a Neonatal Liver-Specific AAV-Mediated Gene Transfer in a Lethal Mouse Model of Crigler-Najjar Syndrome

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F14%3A10282655" target="_blank" >RIV/00216208:11110/14:10282655 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1089/hum.2013.233" target="_blank" >http://dx.doi.org/10.1089/hum.2013.233</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1089/hum.2013.233" target="_blank" >10.1089/hum.2013.233</a>

Result language

angličtina

Original language name

Life-Long Correction of Hyperbilirubinemia with a Neonatal Liver-Specific AAV-Mediated Gene Transfer in a Lethal Mouse Model of Crigler-Najjar Syndrome

Original language description

Null mutations in the UGT1A1 gene result in Crigler-Najjar syndrome type I (CNSI), characterized by severe hyperbilirubinemia and constant risk of developing neurological damage. Phototherapy treatment lowers plasma bilirubin levels, but its efficacy islimited and liver transplantation is required. To find alternative therapies, we applied AAV liver-specific gene therapy to a lethal mouse model of CNSI. We demonstrated that a single neonatal hUGT1A1 gene transfer was successful and the therapeutic effect lasted up to 17 months postinjection. The therapeutic effect was mediated by the presence of transcriptionally active double-stranded episomes. We also compared the efficacy of two different gene therapy approaches: liver versus skeletal muscle transgene expression. We observed that 5-8% of normal liver expression and activity levels were sufficient to significantly reduce bilirubin levels and maintain lifelong low plasma bilirubin concentration (3.1 +/- 1.5 mg/dl). In contrast, skele

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

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Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2014

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Human Gene Therapy

ISSN

1043-0342

e-ISSN

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Volume of the periodical

25

Issue of the periodical within the volume

9

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

844-855

UT code for WoS article

000342155800009

EID of the result in the Scopus database

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