Zusammenfassung
Die Entwicklung von Strategien zur gentherapeutischen Behandlung von Erkrankungen der Leber stellt, aufgrund ihrer zentralen Bedeutung sowohl für Stoffwechselerkrankungen als auch bei metastatischen Tumorerkrankungen, eine große Herausforderung dar. Als Modell für einen angeborenen, überwiegend die Leber betreffenden Stoffwechseldefekt ist die familiäre Hypercholesterinämie von großem Interesse. Die Aufklärung der molekulargenetischen Grundlagen, der Mangel an wirksamen konservativen Therapiemethoden und das relativ einfache Monitoring eines Therapieerfolges sind dabei von ausschlaggebender Bedeutung. Ein klinischer Versuch, unter Einsatz von Retroviren ‘ex vivo’ ein intaktes Gen des humanen LDL-Rezeptors in Leberzellen zu installieren, wurde bereits durchgeführt. Weitere, sowohl virale als auch nichtvirale Vektorsysteme, werden auf ihre Anwendbarkeit zur Gentherapie in der Leber untersucht. Dieser Beitrag beschreibt die sich auf dem Weg zu einer erfolgreichen Gentherapie ergebenden Probleme und umreißt den gegenwärtigen Entwicklungsstand der einzelnen Systeme.
Summary
The developement of strategies for gene therapy in the liver is a challenging task because of its central importance for metabolic disease as well as metastatic tumors. As a model for an inborn disease which particularly affects the liver the familial hypercholesterolemia is of great interest. The understanding of the molecular base, the lack of efficient conservative therapies and the easy monitoring of therapeutic effects are the most important factors for this choice. In the first clinical trial recombinant retrovirus carrying the human LDL-receptor gene were employed in an ex vivo approach to introduce the gene into hepatocytes. Other systems, viral and non-viral in origin, are currently under investigation for their use in gene therapy in the liver. This article describes the problemes which arise on the way to a successful gene therapy and summarizes the current stage of developement of the individual systems.
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Cichon, G. et al. (1995). Möglichkeiten der Gentherapie von Stoffwechselerkrankungen der Leber. In: Beger, H.G., Manns, M.P., Greten, H. (eds) Molekularbiologische Grundlagen der Gastroenterologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79782-8_39
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DOI: https://doi.org/10.1007/978-3-642-79782-8_39
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