Lentiviral Vectors That Express UGT1A1 in Liver and Contain miR-142 Target Sequences Normalize Hyperbilirubinemia in Gunn Rats

Schmitt, Françoise; Remy, Séverine; Dariel, Anne; Flageul, Maude; Pichard, Virginie; Boni, Sébastien; Usal, Claire; Myara, Anne; Laplanche, Sophie; Anegón, Ignacio; Labrune, Philippe; Podevin, Guillaume; Ferry, Nicolas; Nguyen, Tuan Huy

doi:10.1053/j.gastro.2010.05.008

Cited by 34 publications

(18 citation statements)

References 33 publications

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“…This lentiviral vector stringently targets transgene expression to hepatocytes through transcriptional and microRNA (miR)-mediated regulation. We and others have shown the efficacy of this vector in establishing correction of hemophilia B and A in mouse models and of hyperbilirubinemia in rats (12, 16, 17). …”

Section: Introductionmentioning

confidence: 94%

Liver-directed lentiviral gene therapy in a dog model of hemophilia B

et al. 2015

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We investigated the safety and efficacy of liver-directed gene therapy using lentiviral vectors in a large animal model of hemophilia B, and evaluated the risk of insertional mutagenesis in tumor-prone mouse models. We show that gene therapy using lentiviral vectors targeting expression of a canine factor IX transgene to hepatocytes was well-tolerated and provided stable long-term production of coagulation factor IX in dogs with hemophilia B. By exploiting three different mouse models designed to amplify the consequences of insertional mutagenesis, we show that no genotoxicity was detected with these lentiviral vectors. Our findings suggest that lentiviral vectors may be an attractive candidate for gene therapy targeted to the liver and may be useful for the treatment of hemophilia.

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Section: Introductionmentioning

confidence: 94%

Liver-directed lentiviral gene therapy in a dog model of hemophilia B

et al. 2015

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“…However, given the mortality, morbidity, and cost of transplant procedures, there is high motivation to develop alternative approaches including gene therapy (Miranda and Bosma, 2009). A number of preclinical gene therapy studies in the Gunn rat, a natural mutant that has no UGT1A1 activity, have achieved correction in vivo by hepatic gene transfer of the UGT1A1 gene using various vectors, such as viral vectors based on retrovirus (Nguyen et al, 2007), lentivirus (van der Wegen et al, 2006;Schmitt et al, 2010), recombinant simian virus 40 (SV40) virus (Sauter et al, 2000), adenovirus (Askari et al, 1996;Toietta et al, 2005;Dimmock et al, 2011), adeno-associated virus (AAV) (Seppen et al, 2006), and naked plasmid DNA (pDNA) (Danko et al, 2004;Jia and Danko, 2005b).…”

Section: Introductionmentioning

confidence: 99%

Sustained Reduction of Hyperbilirubinemia in Gunn Rats After Adeno-Associated Virus-Mediated Gene Transfer of Bilirubin UDP-Glucuronosyltransferase Isozyme 1A1 to Skeletal Muscle

Pastore

Nusco²,

Vaníková³

et al. 2012

Human Gene Therapy

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“…To overcome this limitation, viral promoters have been replaced by tissue-specifi c mammalian promoter elements. Several liver-specifi c promoters are known and include those of the apolipoprotein A-1 [ 171 ], transthyretin (mTTR.hUGT1A1) [ 172 ], albumin [ 173 ], and α1-antitrypsin (hAAT) gene [ 174 ]. The liver-specifi c promoter of the thyroxin-binding globulin (TBG) gene may display slightly less activity than the widely used CMV (cytomegalovirus) and EF1α (elongation factor 1α) promoters, but TBG has proven to direct long-term exogenous gene expression in the liver [ 175 , 176 ].…”

Section: Hepatocyte-specifi C Promoter Elementsmentioning

confidence: 99%

Gene Therapies for Hepatitis C Virus

Verstegen

Pan

Laan

2015

Advances in Experimental Medicine and Biology

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Hepatitis C virus (HCV) is a leading cause of chronic hepatitis and infects approximately three to four million people per year, about 170 million infected people in total, making it one of the major global health problems. In a minority of cases HCV is cleared spontaneously, but in most of the infected individuals infection progresses to a chronic state associated with high risk to develop liver cirrhosis, hepatocellular cancer, or liver failure. The treatment of HCV infection has evolved over the years. Interferon (IFN)-α in combination with ribavirin has been used for decades as standard therapy. More recently, a new standard-of-care treatment has been approved based on a triple combination with either HCV protease inhibitor telaprevir or boceprevir. In addition, various options for all-oral, IFN-free regimens are currently being evaluated. Despite substantial improvement of sustained virological response rates, some intrinsic limitations of these new direct-acting antivirals, including serious side effects, the risk of resistance development and high cost, urge the development of alternative or additional therapeutic strategies. Gene therapy represents a feasible alternative treatment. Small RNA technology, including RNA interference (RNAi) techniques and antisense approaches, is one of the potentially promising ways to investigate viral and host cell factors that are involved in HCV infection and replication. With this, newly developed gene therapy regimens will be provided to treat HCV. In this chapter, a comprehensive overview guides you through the current developments and applications of RNAi and microRNA-based gene therapy strategies in HCV treatment.

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Lentiviral Vectors That Express UGT1A1 in Liver and Contain miR-142 Target Sequences Normalize Hyperbilirubinemia in Gunn Rats

Cited by 34 publications

References 33 publications

Liver-directed lentiviral gene therapy in a dog model of hemophilia B

Liver-directed lentiviral gene therapy in a dog model of hemophilia B

Sustained Reduction of Hyperbilirubinemia in Gunn Rats After Adeno-Associated Virus-Mediated Gene Transfer of Bilirubin UDP-Glucuronosyltransferase Isozyme 1A1 to Skeletal Muscle

Gene Therapies for Hepatitis C Virus

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