Deciphering entry pathway of NGR-retargeted adenovirus vectors by confocal microscopy
Principal investigator
In the last two decades vectors based on adenoviruses (Ads) became first choice for gene therapy application where short-term gene expression is required. Ads can be de-targeted from their natural receptor and retargeted toward molecule expressed on tissue of interest by genetic modification of adenovirus capsid proteins. Recently we have inserted NGR peptide in fiber and hexon protein and showed that NGR-modified Ads, depending on NGR scaffold, can bind aminopeptidase N or ?vß3 integrin. The objective of this visit is to define the endocytic pathways of NGR-modified adenoviral vectors by using confocal microscopy. This visit would allow me learning new techniques and methods for confocal imaging of adenoviruses and transferring this knowledge to Ruđer Bošković Institute. The proposed visit would also be the start of the collaboration of our two groups: group led by dr. Andreja Ambriović-Ristov at the Ruđer Bošković Institute and group led by dr. Karim Benihoud at the Institut Gustave Roussy. Results obtained in this project will clarify the mechanism of endocytosis of adenoviruses retargeted by incorporation of NGR and will extend our knowledge on endocytosis mechanisms of retargeted adenoviruses that will enable modeling of new adenovirus vectors retargeted to other molecules as potential targets for tumor gene therapy.