TY  - JOUR
A1  - Hagen, Sven
A1  - Baumann, Tobias
A1  - Wagner, Hanna J.
A1  - Morath, Volker
A1  - Kaufmann, Beate
A1  - Fischer, Adrian
A1  - Bergmann, Stefan
A1  - Schindler, Patrick
A1  - Arndt, Katja Maren
A1  - Mueller, Kristian M.
T1  - Modular adeno-associated virus (rAAV) vectors used for cellular virus-directed enzyme prodrug therapy
JF  - Scientific reports
N2  - 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).
Y1  - 2014
U6  - https://doi.org/10.1038/srep03759
SN  - 2045-2322
VL  - 4
PB  - Nature Publ. Group
CY  - London
ER  -