Improved efficacy and reduced toxicity by ultrasound-guided intrahepatic injections of helper-dependent adenoviral vector in Gunn rats

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F13%3A10192305" target="_blank" >RIV/00216208:11110/13:10192305 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1089/hgtb.2013.108" target="_blank" >http://dx.doi.org/10.1089/hgtb.2013.108</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1089/hgtb.2013.108" target="_blank" >10.1089/hgtb.2013.108</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Improved efficacy and reduced toxicity by ultrasound-guided intrahepatic injections of helper-dependent adenoviral vector in Gunn rats

Popis výsledku v původním jazyce

Crigler-Najjar syndrome type I is caused by mutations of the uridine diphospho-glucuronosy] transferase lAI (UGT1A1) gene resulting in life-threatening increase of serum bilirubin. Life-long correction of hyperbilirubinemia was previously shown with intravenous injection of high doses of a helper-dependent adenoviral (HDAd) vector cxpressing UGT1A1 in the Gunn rat, the animal model of Crigler-Najjar syndrome. I lowever, such high vector doses can activate an acute and potentially lethal inflammatory response with elevated serum interleukin-6 (IL-6). To overcome this obstacle, we investigated safety and efficacy of direct injections of low HDAd doses delivered directly into the liver parenchyma of Gunn rats. Direct hepatic injections performed by eitherlaparotomy or ultrasound-guided percutaneous injections were compared with the same doses given by intravenous injections. A greater reduction of hyperbilirubinemia and inereased conjugated bilirubin in hile were achieved with 1 x 1011 v

Název v anglickém jazyce

Improved efficacy and reduced toxicity by ultrasound-guided intrahepatic injections of helper-dependent adenoviral vector in Gunn rats

Popis výsledku anglicky

Crigler-Najjar syndrome type I is caused by mutations of the uridine diphospho-glucuronosy] transferase lAI (UGT1A1) gene resulting in life-threatening increase of serum bilirubin. Life-long correction of hyperbilirubinemia was previously shown with intravenous injection of high doses of a helper-dependent adenoviral (HDAd) vector cxpressing UGT1A1 in the Gunn rat, the animal model of Crigler-Najjar syndrome. I lowever, such high vector doses can activate an acute and potentially lethal inflammatory response with elevated serum interleukin-6 (IL-6). To overcome this obstacle, we investigated safety and efficacy of direct injections of low HDAd doses delivered directly into the liver parenchyma of Gunn rats. Direct hepatic injections performed by eitherlaparotomy or ultrasound-guided percutaneous injections were compared with the same doses given by intravenous injections. A greater reduction of hyperbilirubinemia and inereased conjugated bilirubin in hile were achieved with 1 x 1011 v

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2013

Kód důvěrnosti údajů

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

Název periodika

Human gene therapy methods

ISSN

1946-6536

e-ISSN

—

Svazek periodika

24

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

321-327

Kód UT WoS článku

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EID výsledku v databázi Scopus

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