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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Vectores > DA - CIMA - Terapia génica y Hepatología - Vectores - Artículos de revista >

In vitro and in vivo comparative study of chimeric liver-specific promoters
Authors: Kramer, M.G. (María Gabriela)
Barajas, M. (Miguel)
Razquin, N. (Nerea)
Berraondo, P. (Pedro)
Rodrigo, M. (Manuel)
Wu, C. (Catherine)
Qian, C. (Cheng)
Fortes, P. (Puri)
Prieto, J. (Jesús)
Keywords: Transcriptional targeting
Gene therapy
Liver-specific promoters
Hydrodynamics-based transfection
Polyethylenimine
Long-term expression
Issue Date: 2003
Publisher: Nature Publishing Group
Publisher version: http://www.nature.com/mt/journal/v7/n3/full/mt200356a.html
ISSN: 1525-0024
Citation: Kramer MG, Barajas M, Razquin N, Berraondo P, Rodrigo M, Wu C, et al. In vitro and in vivo comparative study of chimeric liver-specific promoters. Mol Ther 2003 Mar;7(3):375-385.
Abstract
Targeting therapeutic genes to the liver is essential to improve gene therapy protocols of hepatic diseases and of some hereditary disorders. Transcriptional targeting can be achieved using liver-specific promoters. In this study we have made chimeric constructs combining promoter and enhancer regions of the albumin, alpha 1-antitrypsin, hepatitis B virus core protein, and hemopexin genes. Tissue specificity, activity, and length of gene expression driven from these chimeric regulatory sequences have been analyzed in cultured cells from hepatic and nonhepatic origin as well as in mice livers and other organs. We have identified a collection of liver-specific promoters whose activities range from twofold to less than 1% of the CMV promoter in human hepatoma cells. We found that the best liver specificity was attained when both enhancer and promoter sequences of hepatic genes were combined. In vivo studies were performed to analyze promoter function during a period of 50 days after gene transfer to the mouse liver. We found that among the various chimeric constructs tested in this work, the alpha1-antitrypsin promoter alone or linked to the albumin or hepatitis B enhancers is the most potent in directing stable gene expression in liver cells.
Permanent link: http://hdl.handle.net/10171/23260
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Vectores - Artículos de revista

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