@article{FeinerTeschnerTeschneretal.2019,
  author    = {Feiner, Rebecca Christine and Teschner, Julian and Teschner, Kathrin E. and Radukic, Marco T. and Baumann, Tobias and Hagen, Sven and Hannappel, Yvonne and Biere, Niklas and Anselmetti, Dario and Arndt, Katja Maren and M{\"u}ller, Kristian Mark},
  title     = {rAAV Engineering for Capsid-Protein Enzyme Insertions and Mosaicism Reveals Resilience to Mutational, Structural and Thermal Perturbations},
  series = {International journal of molecular sciences},
  volume    = {20},
  journal   = {International journal of molecular sciences},
  number    = {22},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {1422-0067},
  doi       = {10.3390/ijms20225702},
  pages     = {19},
  year      = {2019},
  abstract  = {Recombinant adeno-associated viruses (rAAV) provide outstanding options for customization and superior capabilities for gene therapy. To access their full potential, facile genetic manipulation is pivotal, including capsid loop modifications. Therefore, we assessed capsid tolerance to modifications of the structural VP proteins in terms of stability and plasticity. Flexible glycine-serine linkers of increasing sizes were, at the genetic level, introduced into the 587 loop region of the VP proteins of serotype 2, the best studied AAV representative. Analyses of biological function and thermal stability with respect to genome release of viral particles revealed structural plasticity. In addition, insertion of the 29 kDa enzyme beta-lactamase into the loop region was tested with a complete or a mosaic modification setting. For the mosaic approach, investigation of VP2 trans expression revealed that a Kozak sequence was required to prevent leaky scanning. Surprisingly, even the full capsid modification with beta-lactamase allowed for the assembly of capsids with a concomitant increase in size. Enzyme activity assays revealed lactamase functionality for both rAAV variants, which demonstrates the structural robustness of this platform technology.},
  language  = {en}
}
@article{HagenBaumannWagneretal.2014,
  author    = {Hagen, Sven and Baumann, Tobias and Wagner, Hanna J. and Morath, Volker and Kaufmann, Beate and Fischer, Adrian and Bergmann, Stefan and Schindler, Patrick and Arndt, Katja Maren and Mueller, Kristian M.},
  title     = {Modular adeno-associated virus (rAAV) vectors used for cellular virus-directed enzyme prodrug therapy},
  series = {Scientific reports},
  volume    = {4},
  journal   = {Scientific reports},
  publisher = {Nature Publ. Group},
  address   = {London},
  issn      = {2045-2322},
  doi       = {10.1038/srep03759},
  pages     = {11},
  year      = {2014},
  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).},
  language  = {en}
}
@article{HagenMattayRaeuberetal.2014,
  author    = {Hagen, Sven and Mattay, Dinah and Raeuber, Christina and Mueller, Kristian M. and Arndt, Katja Maren},
  title     = {Characterization and inhibition of AF10-mediated interaction},
  series = {Journal of peptide science},
  volume    = {20},
  journal   = {Journal of peptide science},
  number    = {6},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {1075-2617},
  doi       = {10.1002/psc.2626},
  pages     = {385 -- 397},
  year      = {2014},
  abstract  = {The non-random chromosomal translocations t(10;11)(p13;q23) and t(10;11)(p13;q14-21) result in leukemogenic fusion proteins comprising the coiled coil domain of the transcription factor AF10 and the proteins MLL or CALM, respectively, and subsequently cause certain types of acute leukemia. The AF10 coiled-coil domain, which is crucial for the leukemogenic effect, has been shown to interact with GAS41, a protein previously identified as the product of an amplified gene in glioblastoma. Using sequential synthetic peptides, we mapped the potential AF10/GAS41 interaction site, which was subsequently be used as scaffold for a library targeting the AF10 coiled-coil domain. Using phage display, we selected a peptide that binds the AF10 coiled-coil domain with higher affinity than the respective coiled-coil region of wild-type GAS41, as demonstrated by phage ELISA, CD, and PCAs. Furthermore, we were able to successfully deploy the inhibitory peptide in a mammalian cell line to lower the expression of Hoxa genes that have been described to be overexpressed in these leukemias. This work dissects molecular determinants mediating AF10-directed interactions in leukemic fusions comprising the N-terminal parts of the proteins MLL or CALM and the C-terminal coiled-coil domain of AF10. Furthermore, it outlines the first steps in recognizing and blocking the leukemia-associated AF10 interaction in histiocytic lymphoma cells and therefore, may have significant implications in future diagnostics and therapeutics. Copyright (c) 2014 European Peptide Society and John Wiley \& Sons, Ltd.},
  language  = {en}
}