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Connectivity
| Project leader |
Majhen Dragomira |
| Project co-leader: |
Karim Benihoud, PhD |
| Administering organization: |
Ruđer Bošković Institute, Bijenička 54, Zagreb, Croatia |
| Partner Institution/Company: |
Institute Gustave Roussy, UMR 8203, Vectorologie et thérapeutiques anticancéreuses |
| Grant type: |
2A |
| Project title: |
Deciphering entry pathway of NGR-retargeted adenovirus vectors by confocal microscopy |
| Project summary: |
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.
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| Hrvatski sažetak: |
U posljednjih dvadesetak godina vektori temeljeni na adenovirusu postali su prvi izbor u genskoj terapiji u slučaju kada je potrebna kratkotrajna ekspresija unešenog transgena. Genetskim promjenama proteina kapside adenovirusa, moguće je dokinuti vezanje adenovirusa na njegov primarni receptor i preusmjeriti infekciju adenovirusa na novu molekulu specifično eksprimiranu u ciljnom tkivu. Nedavno smo ugradili NGR slijed u proteine vlakna ili heksona adenovirusa, te pokazali da se NGR-om preusmjereni adenovirusi, ovisno o aminokiselinskoj okolini NGR slijeda, mogu vezati na aminopeptidazu N i/ili ?vß3 integrin.
Cilj ovog posjeta je otkrivanje mehanizma endocitoze NGR-om preusmjerenih adenovirusnih vektora korištenjem konfokalne mikroskopije. Predloženi posjet omogućit će mi usvajanje novih tehnika i metoda namjenjenih unutrastaničnom praćenju adenovirusa, te prenošenje usvojenog znanja na Institut Ruđer Bošković.
Predloženi posjet će također biti početak suradnje hrvatske grupe koju na Institutu Ruđer Bošković vodi dr sc Andreja Ambriović Ristov te grupe koju na Institutu Gustave Roussy vodi dr sc Karim Benihoud.
Rezultati dobiveni ovim istraživanjem razjasnit će mehanizam endocitoze adenovirusa preusmjerenih ugradnjom NGR slijeda. Samim time proširiti ćemo naše opće znanje o mehanizmima endocitoze preusmjerenih adenovirusa što će nam omogućiti daljnji dizajn novih adenovirusnih vektora preusmjerenih na neke druge potencijalne ciljne molekule za gensku terapiju tumora.
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| Amount requested from UKF: |
72.000,00 HRK |
| Amount of matching funding: |
14.400,00 HRK |
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