Liver-specific Factor VIII expression by microRNA-regulated lentiviral vector

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A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice.

A longstanding goal for the treatment of hemophilia B is the development of a gene transfer strategy that can maintain sustained production of clotting factor IX (F.IX) in the absence of an immune response. To this end, we have sought to use lentiviral vectors (LVs) as a means for systemic gene transfer. Unfortunately, initial evaluation of LVs expressing F.IX from hepatocyte-specific promoters...

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Delivery of Factor VIII Gene into Skeletal Muscle Cells Using Lentiviral Vector

PURPOSE This study was designed to investigate whether transduction of lentiviral vectors (LV) carrying human coagulation factor VIII (hFVIII) cDNA into skeletal muscle could increase circulating hFVIII concentrations. MATERIALS AND METHODS A LV containing bacterial LacZ gene as a control or human FVIII gene was intramuscularly administered into the thigh muscle of 5 weeks old Sparague-Dawley...

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Construction and identification of a human liver specific microRNA eukaryotic expression vector.

MiR-122 is one of the non-coding RNAs which showed its effects on the lipo-metablism, virus infection and HCC forming through regulation of liver gene expression. Its eukaryotic expression vector was constructed by using pSuper which was widely applied in the siRNA expression. The precursor of human miR-122 gene was amplified by polymerase chain reaction (PCR) from the human genomic DNA. The po...

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Human coagulation factor VIII domain-specific recombinant polypeptide expression

BACKGROUND Hemophilia A is caused by heterogeneous mutations in F8. Coagulation factor VIII (FVIII), the product of F8, is composed of multiple domains designated A1-A2-B-A3-C1-C2. FVIII is known to interact with diverse proteins, and this characteristic may be important for hemostasis. However, little is known about domain-specific functions or their specific binding partners. METHODS To det...

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Persistent expression of factor VIII in vivo following nonprimate lentiviral gene transfer.

Hemophilia A is a clinically important coagulation disorder caused by the lack or abnormality of plasma coagulation factor VIII (FVIII). Gene transfer of the FVIII cDNA to hepatocytes using lentiviral vectors is a potential therapeutic approach. We investigated the efficacy of feline immunodeficiency virus (FIV)-based vectors in targeting hepatocytes and correcting FVIII deficiency in a hemophi...

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ژورنال

عنوان ژورنال: Japanese Journal of Thrombosis and Hemostasis

سال: 2011

ISSN: 1880-8808,0915-7441

DOI: 10.2491/jjsth.22.377