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DNA electrotransfer of plasmids coding for antiangiogenic factors as a proof of principle of non-viral gene therapy for the treatment of skin disease


The ANGIOSKIN consortium wants to bring the proof of concept that therapeutic genes can be safely delivered to skin by DNA electrotransfer (electrogenetherapy) in order to prevent or to treat acquired or inherited skin diseases. ANGIOSKIN proposal is based on the results of the 5th FP CLINIPORATOR project (analysis of the mechanisms of DNA electrotransfer and elaboration of a CE labelled pulse generator) and of the 5th FP ESOPE project (preparation of the Standard Operating Procedures of Electrogenetherapy, electrotransferring a reporter gene in humans), and on a proprietary gene coding for a potent human antiangiogenic factor. This factor is the disintegrin fragment of the Metargidin, also referred as AMD-15 (MDC 15 in mouse), and it specifically binds to t he avß3 and a5ß1 integrins involved in angiogenic processes. ANGIOSKIN consortium will: - Electrotransfer the proprietary therapeutic antiangiogenesis gene to melanoma cutaneous metastasis in humans, using the procedures validated in ESOPE project, to show its clinical efficacy; non invasive biophysical methods (e.g. Doppler ultrasonography) will be used to monitor the angioangiogenic effects; - Develop new specific electrodes for skin lesions treatment, based on arrays of hollow microneedles allowing both DNA and electric pulse delivery, and requiring the use of micromechanics ans microfluidics techniques; - Validate the electrodes (safety, efficacy) on normal skin in animals, and analyse the effects of the electrotransfer of the antioangiogenetic factor on models of skin disease related to excessive angiogenesis (models of psoriasis), using non nonvasive biophysical as well as histological methods to follow changes in the vascularization of the lesion; - Finally, electrotransfer the therapeutic gene to a be nign lesion (psoriasis) in humans as a proof of concept of the use of non-viral gene therapy to treat acquired or inherited skin diseases.

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