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.

Journal Article | Published | English

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Abstract
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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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.
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).
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57 References

Data provided by Europe PubMed Central.

Part:pSB1C3. Registry of Standard Biological Parts. 2013-12-17
AUTHOR UNKNOWN, 0
Polyethylenimine, a cost-effective transfection reagent
AUTHOR UNKNOWN, 2006
Fast and reliable titration of recombinant adeno-associated virus type-2 using quantitative real-time PCR.
Rohr UP, Wulf MA, Stahn S, Steidl U, Haas R, Kronenwett R., J. Virol. Methods 106(1), 2002
PMID: 12367732
Quantitative real-time PCR for titration of infectious recombinant AAV-2 particles.
Rohr UP, Heyd F, Neukirchen J, Wulf MA, Queitsch I, Kroener-Lux G, Steidl U, Fenk R, Haas R, Kronenwett R., J. Virol. Methods 127(1), 2005
PMID: 15893564
Genetic analysis of hyperproduction of epidermal growth factor receptors in human epidermoid carcinoma A431 cells.
Shimizu N, Kondo I, Gamou S, Behzadian MA, Shimizu Y., Somat. Cell Mol. Genet. 10(1), 1984
PMID: 6322359

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