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  - 
TY  - JOUR
A1  - Kuekenshoener, Tim
A1  - Hagemann, Urs B.
A1  - Wohlwend, Daniel
A1  - Raeuber, Christina
A1  - Baumann, Tobias
A1  - Keller, Sandro
A1  - Einsle, Oliver
A1  - Mueller, Kristian M.
A1  - Arndt, Katja Maren
T1  - Analysis of Selected and Designed Chimeric D- and L-alpha-Helix Assemblies
JF  - Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences
N2  - D-Peptides have been attributed pharmacological advantages over regular L-peptides, yet design rules are largely unknown. Based on a designed coiled coil-like D/L heterotetramer, named L-Base/D-Acid, we generated a library offering alternative residues for interaction with the D-peptide. Phage display selection yielded one predominant peptide, named HelixA, that differed at 13 positions from the scaffold helix. In addition to the observed D-/L-heterotetramers, ratio-dependent intermediate states were detected by isothermal titration calorimetry. Importantly, the formation of the selected HelixA/D-Acid bundle passes through fewer intermediate states than L-Base/D-Acid. Back mutation of HelixA core residues to L-Base (HelixLL) revealed that the residues at e/g-positions are responsible for the different intermediates. Furthermore, a Val-core variant (PeptideVV) was completely devoid of binding D-Acid, whereas an Ile-core helix (HelixII) interacted with D-Acid in a significantly more specific complex than L-Base.
Y1  - 2014
U6  - https://doi.org/10.1021/bm5006883
SN  - 1525-7797
SN  - 1526-4602
VL  - 15
IS  - 9
SP  - 3296
EP  - 3305
PB  - American Chemical Society
CY  - Washington
ER  -