John Dangerfield -  Nanovirology      

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Research Institute of Virology and Biomedicine
Christian Doppler Laboratory for Gene Therapeutic Vector Development
University of Veterinary Medicine, Vienna, Austria.

The Nano-Viro Team
Group Leader: John Dangerfield
Post-docs: Christoph Metzner, Stefanie Rungaldier
PhD students: Meike Mostegl, Matthias Müllner
Contact:
john.dangerfield@vu-wien.ac.at

Nanotechnology Enhanced Retroviral Vectors for Cancer Gene Therapy
The success of the severe combined immunodeficiency-X1 (X-SCID) trials has arguably shown retroviral vectors (RV) to be the most promising viral gene delivery tools. However, these results were achieved in an ex vivo setting and for the treatment of many diseases, such as cancer, it will be necessary to tackle the in vivo scenario. Unfortunately, therapeutically ineffective in vivo transduction levels still cloud the potential use for RV as efficient gene delivery vehicles as a result of low percentages of applied virus reaching the target tissue. This can be due to unspecific sticking and filtration of virus in capillary beds and to non-target cells, and also because of a general dilution of the viral particles in the comparatively high volume of circulating blood. With such infection efficiencies, the step to an immuno-competent system seems far away when considering the many types of potential antiviral immune responses. In order to overcome these challenging issues we have designed several distinct approaches based on bringing nano- and bionano technologies together with state-of-the-art retroviral technology.


Figure 1. The concept of MagnoVirus. Magnetic nanoparticles (MNP) are associated with therapeutic RV allowing magnetic targeting in vitro and in vivo. Several novel concepts to attach MNP to virus by bridging the bio-mineral interface are currently being tested. Virus-MNP complexes can be protected from the patient’s immune system without affecting the gene transduction efficiency using the process of PEGylation.

In collaboration with experts in Austria and the United States we are also currently working on the development of hybrid organic/inorganic nano electro-mechanical systems (bio-NEMS). Such bio-NEMS have the potential to act as mobile drug or gene delivery tools in biological systems.