Auszug
Die spezifische Inhibition der Expression eines Zielgens ist sowohl für funktionelle Untersuchungen als auch für therapeutische Anwendungen von großer Bedeutung. Ende der 1970er Jahre wurde erstmalig gezeigt, dass Antisense-Oligonukleotide (AS-ONs) aus DNA-Monomeren durch Hybridisierung an eine komplementäre RNA deren Funktion blockieren können (Zamecnik u. Stephenson 1978). Kurze Zeit später wurden RNA-Moleküle entdeckt, die die Umesterung oder Spaltung von Ziel-RNAs katalysieren (Cech et al. 1981; Kruger et al. 1982; Guerrier-Takada et al. 1983). Diese Ribonukleinsäuren mit enzymatischer Aktivität werden als Ribozyme bezeichnet. Antisense-Oligonukleotide und Ribozyme hat man in zahlreichen Studien erfolgreich eingesetzt, um die Synthese eines Genprodukts spezifisch auf RNA-Ebene in Zellkulturversuchen oder in Tiermodellen zu inhibieren. Aus den entstehenden „loss-of-function“-Phänotypen konnten Rückschlüsse auf die Bedeutung des Zielgens gezogen werden.Aufgrund dieser Erfolge wurden klinische Studien initiiert, in denen die Expression schädlicher Gene bei Tumorerkrankungen, viralen Infektionen oder entzündlichen Erkrankungen verhindert werden sollte.
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Kurreck, J., Schubert, S., Erdmann, V.A. (2008). Antisenes-, Ribozym- und RNA-Interferenz-Strstegien: Methoden des posttranskriptionellen Gene Silencing in der Molekularen Medizin. In: Ganten, D., Ruckpaul, K. (eds) Grundlagen der Molekularen Medizin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-69414-4_18
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