Zusammenfassung
Die großen Fortschritte in der Gentechnik und der Genom-Editierung von Nutztieren haben deren Einsatz für biomedizinische Anwendungen erheblich ausgeweitet. Die bemerkenswertesten Beispiele sind maßgeschneiderte Großtiermodelle für die translationale Medizin, Schweinezellen, -gewebe und -organe für die Xenotransplantation und die Herstellung von pharmazeutischen Proteinen in transgenen Großtieren. Die Umsetzung neuer Entdeckungen von der Grundlagenforschung in die klinische Anwendung ist ein langwieriger, oft ineffizienter und kostspieliger Prozess. Geeignete Tiermodelle sind entscheidend für den Erfolg der translationalen Forschung. Obwohl Nagetiermodelle weit verbreitet sind, bilden sie die menschliche Krankheit oft nicht genau ab. Daher werden zusätzliche Tiermodelle benötigt, die Aspekte der menschlichen Anatomie und Physiologie genauer nachbilden. Es wurden mehrere gentechnisch veränderte Schweinemodelle entwickelt, von denen viele die menschlichen Krankheitsmechanismen und Phänotypen besser darstellen als die bestehenden Nagetiermodelle. Darüber hinaus sind gentechnisch veränderte kleine Wiederkäuer und Kaninchen interessante Modelle für bestimmte Krankheiten. Schweine sind die vielversprechendsten Spendertiere für die Xenotransplantation. Da mehrere genetische Veränderungen erforderlich sind, um eine Abstoßung durch das Immunsystem zu verhindern, physiologische Inkompatibilitäten von Xeno-Organen zu überwinden und potenzielle Risikofaktoren wie porcine endogene Retroviren (PERV) zu eliminieren, beschleunigt das Genome Editing die Fortschritte in diesem Bereich. Nicht zuletzt ist die gentechnische Veränderung großer Tierarten als Bioreaktoren für die Herstellung pharmazeutischer Proteine nach wie vor eine interessante Option, auch wenn nur wenige derartige Produkte auf dem Markt sind. Zusammenfassend lässt sich sagen, dass gentechnisch veränderte Großtiere eine immer wichtigere Rolle in der Biomedizin spielen. Insbesondere können genetisch maßgeschneiderte Großtiermodelle dazu beitragen, die Lücke zwischen Proof-of-Concept-Studien in Nagetiermodellen und klinischen Versuchen an menschlichen Patienten zu schließen.
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Danksagung
Unsere Studien zur Entwicklung von Großtiermodellen werden von der Deutschen Forschungsgemeinschaft, dem Bundesministerium für Bildung und Forschung, der Mildred-Scheel-Stiftung der Deutschen Krebshilfe, der Bayerischen Forschungsgemeinschaft und dem Mukoviszidose Institut gemeinnützige Gesellschaft für Forschung und Therapieentwicklung mbH unterstützt. Die Autoren sind Mitglieder der EU COST Action BM1308.
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Wolf, E., Kind, A., Aigner, B., Schnieke, A. (2023). Gentechnisch veränderte Großtiere in der Biomedizin. In: Niemann, H., Wrenzycki, C. (eds) Biotechnologie bei Nutztieren 2. Springer, Cham. https://doi.org/10.1007/978-3-031-26042-1_9
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