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Gene Therapy: Modeling Synthetic DNA Delivery Systems

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.

Field of science

  • /medical and health sciences/medical biotechnology/genetic engineering/gene therapy

Call for proposal

FP7-PEOPLE-2009-RG
See other projects for this call

Funding Scheme

MC-IRG - International Re-integration Grants (IRG)

Coordinator

PANEPISTIMIO KRITIS
Address
University Campus Gallos
74100 Rethimno
Greece
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 100 000
Administrative Contact
Eleni Karkanaki (Ms.)