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Targeting EGFR with metabolically biotinylated fiber-mosaic adenovirus

Gene Therapy volume 14, pages 627–637 (2007)Cite this article

Abstract

Adenovirus (Ad)-based vectors are useful gene delivery vehicles for a variety of applications. Despite their attractive properties, many in vivo applications require modulation of the viral tropism. Targeting approaches applied to adenoviral vectors included genetic modification of the viral capsid, controlled expression of the transgene and combinatorial approaches that combine two or more targeting elements in single vectors. Most of these studies confirmed successful retargeting in cell cultures, however, in vivo gains of targeted adenoviral vectors have not been widely demonstrated. We have developed a combinatorial retargeting approach utilizing metabolically biotinylated Ad, where the biotin acceptor peptide was incorporated in one of the fibers in a dual fiber viral particle resulting in metabolically biotinylated fiber-mosaic Ad (mBfMAd). We have utilized this vector in complex with epidermal growth factor (EGF)-Streptavidin to retarget fiber-mosaic virus to EGF receptor (EGFR) expressing cells in vitro and confirmed an increased infectivity of the retargeting complex. Most importantly, the utility of this strategy was demonstrated in vivo in two distinct animal models. In both models tested, retargeted mBfMAd demonstrated an increased ratio of gene expression in target tissues compared to the liver expression profile. Thus, metabolically biotinylated fiber-mosaic virus in combination with appropriate adapters can be successfully exploited for adenoviral retargeting strategies.

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Acknowledgements

We thank Joel Glasgow and Alex Pereboev for proofing the manuscript and helpful critique. This study was supported, in part, by NIH grants RO1CA083821-06, 1P01HL076540, 1P01CA104177-01A2, CA075930-07 and DOD grant W81XWH-05-1-0035 and Muscular Dystrophy Association.

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Authors and Affiliations

  1. Division of Human Gene Therapy, Departments of Medicine, Obstetric and Gynecology, Pathology and Surgery, Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL, USA

    L Pereboeva, S Komarova, J Roth & D T Curiel

  2. Department of Pathology, Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL, USA

    S Ponnazhagan

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  1. L Pereboeva
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  2. S Komarova
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  3. J Roth
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  4. S Ponnazhagan
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  5. D T Curiel
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Correspondence to D T Curiel.

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Pereboeva, L., Komarova, S., Roth, J. et al. Targeting EGFR with metabolically biotinylated fiber-mosaic adenovirus. Gene Ther 14, 627–637 (2007). https://doi.org/10.1038/sj.gt.3302916

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