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ANGIOSKIN<br />
DNA Electrotransfer of Plasmids<br />
Coding for Antiangiogenic<br />
Factors as a Proof of Principle<br />
of Non-Viral Gene Therapy for<br />
the Treatment of Skin Disease<br />
Summary<br />
Keywords | Gene therapy | non-viral gene therapy | dermatology | biomedical engineering | electropermeabilisation |<br />
electroporation | DNA electrotransfer | antiangiogenesis | cancer treatment | new therapies | electric pulses |<br />
skin diseases | naked DNA | medical instrumentation |<br />
The Angioskin consortium wants to bring the proof of concept<br />
that therapeutic genes can be safely delivered to skin<br />
by DNA electrotransfer (electrogenetherapy) in order to<br />
prevent or to treat acquired or inherited skin diseases. The<br />
Angioskin proposal is based on the results of the Fifth<br />
Framework Programme’s (FP5) Cliniporator project (the<br />
analysis of the mechanisms of DNA electrotransfer and<br />
elaboration of a CE labelled pulse generator) and of the<br />
FP5’s ESOPE project (the preparation of the standard operating<br />
procedures of Electrogenetherapy, electrotransferring<br />
a reporter gene in humans), and on a gene coding for a potent<br />
human antiangiogenic factor. This factor specifi cally<br />
binds to the αvβ3 and α5β1 integrins involved in angiogenic<br />
processes.<br />
Problem<br />
Non-viral gene transfer for the treatment of acquired or<br />
inherited skin diseases.<br />
Aim<br />
• To electrotransfer proprietary therapeutic antiangiogenesis<br />
genes to cutaneous metastases in humans, using<br />
the procedures validated in the ESOPE project, to show<br />
its clinical effi cacy; non-invasive biophysical methods<br />
will be used to monitor the antiangiogenic eff ects.<br />
• To develop new specifi c electrodes for the treatment of<br />
skin lesions.<br />
• To validate the electrodes (safety, effi cacy) on normal<br />
skin in animals, and analyse the eff ects of the electrotransfer<br />
of the antiangiogenetic factor on models of skin<br />
disease related to excessive angiogenesis, using noninvasive<br />
biophysical as well as histological methods to<br />
follow changes in the vascularisation of the lesion.<br />
• Finally, to electrotransfer the therapeutic gene to<br />
a benign lesion in humans as a proof of concept of the<br />
use of non-viral gene therapy to treat acquired or inherited<br />
skin diseases.<br />
Expected results<br />
Electrodes, pulse generators, procedures, proof of concept<br />
of a new therapeutic approach, clinical validation of an<br />
antiangiogenic factor.<br />
Potential applications<br />
• <strong>Research</strong><br />
• Biotechnologies<br />
• Medicine<br />
162 CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
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