GENETHESIS

Gene Therapy: Modeling Synthetic DNA Delivery Systems

Coordinatore	PANEPISTIMIO KRITIS    more  Organization address address: UNIVERSITY CAMPUS GALLOS city: RETHIMNO postcode: 74100 contact info Titolo: Ms. Nome: Eleni Cognome: Karkanaki Email: send email Telefono: +30 2810 393163 Fax: +30 2810 393130
Nazionalità Coordinatore	Greece [EL]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2009-RG
Funding Scheme	MC-IRG
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-12-01   -   2016-06-01

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	PANEPISTIMIO KRITIS  Organization address address: UNIVERSITY CAMPUS GALLOS city: RETHIMNO postcode: 74100 contact info Titolo: Ms. Nome: Eleni Cognome: Karkanaki Email: send email Telefono: +30 2810 393163 Fax: +30 2810 393130	EL (RETHIMNO)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'Gene delivery techniques offer great hope in developing effective therapies (gene therapies) for serious human diseases. Currently the major challenge in clinical trials is the development of both safe and efficient DNA delivery systems (vectors). Synthetic vectors appear to be safer and more versatile but have significantly lower delivery efficiency than their viral counterparts. In this project we propose a novel molecular-level numerical approach to investigate and determine the properties of synthetic vectors that maximize gene delivery efficiency. We will focus on dendrimers, one of the most promising synthetic polymer vectors under consideration in clinical trials. The specific gene delivery stages to be studied are (1) DNA/polymer complex (polyplex) formulation, (2) polyplex binding to cell membrane, (3) polyplex dissociation to release the DNA, and finally (4) the nuclear entry of DNA. To realistically represent both structure and dynamics over the great length and time scales of the system, we will use two well-established, parallel, coarse-grained molecular dynamic simulators: LAMMPS (large-scale atomic/molecular massively parallel simulator) and MHR (molecular high roller). Appropriate code modifications and extensions will be also incorporated to meet project needs and maximize the simulation’s efficiency. The major aim of this study will be the development of an on-line database of polyplex structures, providing their properties in the different stages of gene delivery. The anticipated results of this project will provide a quantitative description of the mechanisms involved in gene delivery and can also be a rational design tool for the next generation of efficient synthetic vectors. The proposed research is a multidisciplinary and novel numerical study that will hopefully pave the way toward new computer-based approaches in gene therapy.'