One Two
You are here: Home About us FOR 917 Subproject 2

Adenoviral targeting by magnetic nanoparticles to the vasculature - Anton/Plank

Recombinant adenoviral vectors (adv) are commonly used in different fields of gene therapy in pre-clinical and clinical settings. High transduction efficiency and their non-inserting genome make them an attractive tool for gene delivery in vitro and in vivo. Due to their broad host spectrum targeting of adv to a specific organ or tissue still remains challenging.

The aim of the proposed research is the development of nanomagneto-based strategies for targeted delivery of adenoviral vectors in the cardiovascular system. To this extent complexes of adv and magnetic nanoparticles (MNP) (P7) will be produced and analyzed with respect to their ability of transducing different cell types of the cardiovascular system (P1, P4, P5). Targeting will be achieved by use of magnetic vector compositions with binding specificity for endothelial cells and progenitor cells, cardiomyoblasts and mesenchymal stem cells and will be  ompared to fiber modified adv and/or transcriptional targeting. The different formulations will be analyzed in vitro under static as well as flow conditions. Influence of type, number and position of magnets (P6) will be assessed. Optimized transducing conditions will be analyzed in an ex-vivo vascular graft perfusion model (P1, P5) and in vivo after intra-myocardial injection into ischemic rat hearts or a rabbit hind limb ischemia model.

In the long term perspective magnetic targeting of adv may eliminate vector spill-over to nontarget organs, and thus enable safer use of adv for therapy of cardiovascular disease.

Document Actions