John Dangerfield - Nanovirology
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.