Influence of αvβ3 and αvβ5 integrin silencing on attachment, internalization and transduction with adenoviral vectors

Bardak, Irena (2011) Influence of αvβ3 and αvβ5 integrin silencing on attachment, internalization and transduction with adenoviral vectors. Diploma thesis, Faculty of Science > Department of Biology.

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Abstract

Integrins are cell surface heterodimers composed of α and β subunits. Integrins αvβ3 and αvβ5 bind to extracellular matrix proteins and serve as a secondary receptors in adenovirus type 5 (Ad5) infection. The aim of this work was to investigate the role of αvβ3 and αvβ5 integrins in Ad5 infection using siRNA-mediated gene silencing. We have shown that silencing of β3 integrin subunit in MDA-MB-435S cells decreases the expression of αvβ3, but increases the expression of αvβ5 integrin, which results in increased transduction by wild type Ad5RSVβgal and adenovirus retargeted to αv integrins Ad5RGD4CRSVβgal. Silencing of β5 integrin subunit decreases the expression of αvβ5 integrin and leads to decreased transduction by both, abovementioned Ad5. Silencing of β3 and β5 integrin subunits slightly decreased Ad5RGD4CRSVβgal attachment and internalization. According to that, the observed increased Ad5RSVβgal and Ad5RGD4CRSVβgal transduction in cells transfected with specific β3 siRNA, is not a result of changes in attachment and internalization, but is the consequence of more efficient endosome release. Therefore, expression of αvβ5 integrin is the key factor to predict Ad5 transduction efficacy because it regulates escape from the endosome.

Item Type: Thesis (Diploma thesis)
Keywords: αvβ3, αvβ5, adenovirus, tumor gene therapy
Supervisor: Ambriović Ristov, Andreja
Date: 2011
Number of Pages: 47
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Grozdana Sirotic
Date Deposited: 10 Jun 2014 08:33
Last Modified: 10 Jun 2014 08:33
URI: http://digre.pmf.unizg.hr/id/eprint/2313

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