Targeting adenoviral vectors to cells expressing EGFRvIII using a single chain antibody fused to pIX

Description
Title: Targeting adenoviral vectors to cells expressing EGFRvIII using a single chain antibody fused to pIX
Authors: Lanthier, Robert
Date: 2007
Abstract: Current adenovirus retargeting strategies are unable to target the virus to specific cell types. In this study, we investigated whether fusion of a single-chain antibody, MR1, to the capsid protein IX (pIX) could target the virus to cancer cells expressing EGFRvIII. We show that addition of an endoplasmic reticulum signal peptide to pIX-MR1 significantly increased the ability of the fusion protein to bind its ligand. Use of the human CMV promoter rather than the native pIX promoter permitted a greater accumulation of the protein within the cell. Finally, addition of the HIV-1 Tat NLS caused pIX-MR1 to relocalize to the nucleus, the site of capsid assembly. Taken together, these results provide a foundation to design Ad vectors targeted to specific cells through the use of single-chain antibodies. Ultimately, the development of a tropism modified Ad vector would result in a tailored treatment for a particular acquired genetic disease.
URL: http://hdl.handle.net/10393/27527
http://dx.doi.org/10.20381/ruor-12122
CollectionTh├Ęses, 1910 - 2010 // Theses, 1910 - 2010
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