Somatic Gene Therapy

We develop new treatment methods for currently incurable disorders. We use and develop techniques for viral and non-viral gene transfer (vectors), which allow to efficiently introduce nucleic acids (DNA, RNA) into body cells. Vector-mediated gene transfer should either help to treat specific diseases (somatic gene therapy) or to prevent them as in the case of infectious diseases (genetic vaccination).

In recent years gene therapy has been very successful in clinical studies not only for several genetic but also for malignant diseases. It can be assumed that these new methods will become very important for the treatment of numerous diseases in the future.

Our current research projects include:

  • Oncolytic viruses for tumor therapy
  • Studying the interaction of viral vectors with cellular and extracellular barriers
  • Production of viral vectors: Adenovirus, Adeno-Associated Virus (AAV)
  • Genetic vaccination

 

  1. Wienen W, Nilson R, Allemendingen E, Graumann D, Fiedler E, Bosse-Doenecke E, Kochanek S, Krutzke L.
    Affilin-based retargeting of adenoviral vectors to the epidermal growth factor receptor. Biomater Adv  2023 Jan;144:213208. doi: 10.1016/j.bioadv.2022.213208. Epub 2022 Nov 23. DOI: 10.1016/j.bioadv.2022.213208  
  2. Nilson R, Krutzke L, Wienen F, Rojewski M, Zeplin PH, Funk W, Schrezenmeier H, Kochanek S, Kritzinger A.
    Evaluation of Human Mesenchymal Stromal Cells as Carriers for the Delivery of Oncolytic HAdV-5 to Head and Neck Squamous Cell Carcinomas .Viruses. 2023 Jan; 15(1): 218. Published online 2023 Jan 13. doi: 10.3390/v15010218
  3. Nilson R, Lübbers O, Schmidt CQ, Rojewski M, Zeplin PH, Funk W, Schrezenmeier H, Kritzinger A, Kochanek S, Krutzke L.
    Hexon modification of human adenovirus type 5 vectors enables efficient transduction of human multipotent mesenchymal stromal cells.
    Mol Ther Methods Clin Dev 2022; 25(): 96-110; 
  4. Krutzke L, Rösler R, Allmendinger E, Engler T, Wiese S, Kochanek S. Process- and product-related impurities in the ChAdOx1 nCov-19 vaccine.
    Elife 2022; 11():
  5. Kowarz E, Krutzke L, Külp M, Streb P, Larghero P, Reis J, Bracharz S, Engler T, Kochanek S, Marschalek R. 2022 Jan 27. Vaccine-induced COVID-19 mimicry syndrome. Elife 11:e74974. doi: 10.7554/eLife.74974. PMID: 35084333
  6. Greinacher A, Selleng K, Palankar R, Wesche J, Handtke S, Wolff M, Aurich K, Lalk M, Methling K, Völker U, Hentschker C, Michalik S, Steil L, Reder A, Schönborn L, Beer M, Franzke K, Büttner A, Fehse B, Stavrou EX, Rangaswamy C, Mailer RK, Englert H, Frye M, Thiele T, Kochanek S, Krutzke L, Siegerist F, Endlich N, Warkentin TE, Renné T, 2021. Insights in ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopenia. Blood. doi: 10.1182/blood.2021013231. PMID: 34587242
  7. Nilson, R., Lübbers, O., Weiß, L., Singh, K., Scharffetter-Kochanek, K., Rojewski, M., Schrezenmeier, H., Zeplin, P.H., Funk, W., Krutzke, L., Kochanek, S., Kritzinger, A., 2021. Transduction Enhancers Enable Efficient Human Adenovirus Type 5-Mediated Gene Transfer into Human Multipotent Mesenchymal Stromal Cells. Viruses 13, 1136. doi.org/10.3390/v13061136

  8. Krutzke, L., Allmendinger, E., Hirt, K., Kochanek, S., 2020. Chorioallantoic Membrane Tumor Model for Evaluating Oncolytic Viruses. Hum. Gene Ther. 31, 1100–1113. doi.org/10.1089/hum.2020.04

  9. Krüger-Haag A, Lehmann C, Schmidt E, Sonntag F, Hörer M, Kochanek S. 2019. Evaluation of life cycle defective adenovirus mutants for production of adeno-associated virus vectors. The Journal of Gene Medicine, DOI: 10.1002/jgm.3094
  10. Kritzinger A, Ferger B, Gillardon F, Stierstorfer B, Birk G, Kochanek S, Ciossek T. 2018. Age-related pathology after adenoviral overexpression of the leucine-rich repeat kinase 2 in the mouse striatum. Neurobiology of Aging, DOI: 10.1016/j.neurobiolaging.2018.02.008
  11. Kratzer RF, Espenlaub S, Hoffmeister A, Kron MW, Kreppel F. 2017. Covalent decoration of adenovirus vector capsids with the carbohydrate epitope alphaGal does not improve vector immunogenicity, but allows to study the in vivo fate of adenovirus immunocomplexes. PLoS One 12:e0176852.
  12. Krutzke L, Prill JM, Engler T, Schmidt CQ, Xu Z, Byrnes AP, Simmet T, Kreppel F. 2016. Substitution of blood coagulation factor X-binding to Ad5 by position-specific PEGylation: Preventing vector clearance and preserving infectivity. J Control Release 235:379-392
  13. Emmerling VV, Pegel A, Milian EG, Venereo-Sanchez A, Kunz M, Wegele J, Kamen AA, Kochanek S, Hoerer M. 2016. Rational plasmid design and bioprocess optimization to enhance recombinant adeno-associated virus (AAV) productivity in mammalian cells. Biotechnol J 11:290-297
  14. Emmerling VV, Fischer S, Stiefel F, Holzmann K, Handrick R, Hesse F, Horer M, Kochanek S, Otte K. 2016. Temperature-sensitive miR-483 is a conserved regulator of recombinant protein and viral vector production in mammalian cells. Biotechnol Bioeng 113:830-841
  15. Emmerling VV, Fischer S, Kleemann M, Handrick R, Kochanek S, Otte K. 2016. miR-483 is a self-regulating microRNA and can activate its own expression via USF1 in HeLa cells. Int J Biochem Cell Biol 80:81-86.
  16. Silva AC, Simao D, Kuppers C, Lucas T, Sousa MF, Cruz P, Carrondo MJ, Kochanek S, Alves PM. 2015. Human amniocyte-derived cells are a promising cell host for adenoviral vector production under serum-free conditions. Biotechnol J 10:760-771.
  17. Lucas T, Benihoud K, Vigant F, Schmidt CQ, Bachem MG, Simmet T, Kochanek S. 2015. Hexon modification to improve the activity of oncolytic adenovirus vectors against neoplastic and stromal cells in pancreatic cancer. PLoS One 10:e0117254
  18. Bernhard CA, Ried C, Kochanek S, Brocker T. 2015. CD169+ macrophages are sufficient for priming of CTLs with specificities left out by cross-priming dendritic cells. Proc Natl Acad Sci U S A 112:5461-5466.
  19. Genzel Y, Behrendt I, Rodig J, Rapp E, Kueppers C, Kochanek S, Schiedner G, Reichl U. 2013. CAP, a new human suspension cell line for influenza virus production. Appl Microbiol Biotechnol 97:111-122.
  20. Laakkonen JP, Engler T, Romero IA, Weksler B, Couraud PO, Kreppel F, Kochanek S. 2012. Transcellular targeting of fiber- and hexon-modified adenovirus vectors across the brain microvascular endothelial cells in vitro. PLoS One 7:e45977.
  21. Zong S, Kron MW, Epp C, Engler T, Bujard H, Kochanek S, Kreppel F. 2011. DeltaE1 and high-capacity adenoviral vectors expressing full-length codon-optimized merozoite surface protein 1 for vaccination against Plasmodium falciparum. J Gene Med 13:670-679.
  22. Prill JM, Espenlaub S, Samen U, Engler T, Schmidt E, Vetrini F, Rosewell A, Grove N, Palmer D, Ng P, Kochanek S, Kreppel F. 2011. Modifications of adenovirus hexon allow for either hepatocyte detargeting or targeting with potential evasion from Kupffer cells. Mol Ther 19:83-92.
  23. Kron MW, Espenlaub S, Engler T, Schirmbeck R, Kochanek S, Kreppel F. 2011. miRNA-mediated silencing in hepatocytes can increase adaptive immune responses to adenovirus vector-delivered transgenic antigens. Mol Ther 19:1547-1557.
  24. Stephen SL, Montini E, Sivanandam VG, Al-Dhalimy M, Kestler HA, Finegold M, Grompe M, Kochanek S. 2010. Chromosomal integration of adenoviral vector DNA in vivo. J Virol 84:9987-9994.
  25. Kreppel F, Gackowski J, Schmidt E, Kochanek S. 2005. Combined genetic and chemical capsid modifications enable flexible and efficient de- and retargeting of adenovirus vectors. Mol Ther 12:107-117.
  26. Chuah MK, Schiedner G, Thorrez L, Brown B, Johnston M, Gillijns V, Hertel S, Van Rooijen N, Lillicrap D, Collen D, VandenDriessche T, Kochanek S. 2003. Therapeutic factor VIII levels and negligible toxicity in mouse and dog models of hemophilia A following gene therapy with high-capacity adenoviral vectors. Blood 101:1734-1743.