Modular adeno-associated virus (rAAV) vectors used for cellular virus-directed enzyme prodrug therapy

Hagen S, Baumann T, Wagner HJ, Morath V, Kaufmann B, Fischer A, Bergmann S, Schindler P, Arndt KM, Müller K (2014)
Scientific Reports 4.

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Zeitschriftenaufsatz | Veröffentlicht | Englisch
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Abstract / Bemerkung
The pre-clinical and clinical development of viral vehicles for gene transfer increased in recent years, and a recombinant adeno-associated virus (rAAV) drug took center stage upon approval in the European Union. However, lack of standardization, inefficient purification methods and complicated retargeting limit general usability. We address these obstacles by fusing rAAV-2 capsids with two modular targeting molecules (DARPin or Affibody) specific for a cancer cell-surface marker (EGFR) while simultaneously including an affinity tag (His-tag) in a surface-exposed loop. Equipping these particles with genes coding for prodrug converting enzymes (thymidine kinase or cytosine deaminase) we demonstrate tumor marker specific transduction and prodrug-dependent apoptosis of cancer cells. Coding terminal and loop modifications in one gene enabled specific and scalable purification. Our genetic parts for viral production adhere to a standardized cloning strategy facilitating rapid prototyping of virus directed enzyme prodrug therapy (VDEPT).
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Scientific Reports
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4
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Hagen S, Baumann T, Wagner HJ, et al. Modular adeno-associated virus (rAAV) vectors used for cellular virus-directed enzyme prodrug therapy. Scientific Reports. 2014;4.
Hagen, S., Baumann, T., Wagner, H. J., Morath, V., Kaufmann, B., Fischer, A., Bergmann, S., et al. (2014). Modular adeno-associated virus (rAAV) vectors used for cellular virus-directed enzyme prodrug therapy. Scientific Reports, 4. doi:10.1038/srep03759
Hagen, S., Baumann, T., Wagner, H. J., Morath, V., Kaufmann, B., Fischer, A., Bergmann, S., Schindler, P., Arndt, K. M., and Müller, K. (2014). Modular adeno-associated virus (rAAV) vectors used for cellular virus-directed enzyme prodrug therapy. Scientific Reports 4.
Hagen, S., et al., 2014. Modular adeno-associated virus (rAAV) vectors used for cellular virus-directed enzyme prodrug therapy. Scientific Reports, 4.
S. Hagen, et al., “Modular adeno-associated virus (rAAV) vectors used for cellular virus-directed enzyme prodrug therapy”, Scientific Reports, vol. 4, 2014.
Hagen, S., Baumann, T., Wagner, H.J., Morath, V., Kaufmann, B., Fischer, A., Bergmann, S., Schindler, P., Arndt, K.M., Müller, K.: Modular adeno-associated virus (rAAV) vectors used for cellular virus-directed enzyme prodrug therapy. Scientific Reports. 4, (2014).
Hagen, Sven, Baumann, Tobias, Wagner, Hanna J., Morath, Volker, Kaufmann, Beate, Fischer, Adrian, Bergmann, Stefan, Schindler, Patrick, Arndt, Katja M., and Müller, Kristian. “Modular adeno-associated virus (rAAV) vectors used for cellular virus-directed enzyme prodrug therapy”. Scientific Reports 4 (2014).

4 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

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Ståhl S, Gräslund T, Eriksson Karlström A, Frejd FY, Nygren PÅ, Löfblom J., Trends Biotechnol 35(8), 2017
PMID: 28514998
Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivatives.
Szewczuk M, Boguszewska K, Żebrowska M, Balcerczak E, Stasiak M, Świątkowska M, Błaszczak-Świątkiewicz K., Tumour Biol 39(7), 2017
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