Specific and efficient targeting of adenovirus vectors to macrophages: application of a fusion protein between an adenovirus-binding fragment and avidin, linked to a biotinylated oligonucleotide

The Journal of Gene Medicine
J C Emile GrasK Willems van Dijk

Abstract

The application of serotype 5 adenoviruses (Ad5) in macrophages is hampered by the absence of the endogenous coxsackie adenovirus receptor (CAR). To overcome this limitation, we first generated a linker protein consisting of the virus-binding domain of CAR and the C-terminus of avidin. Second, to target macrophages, this linker protein was equipped with the biotinylated (bio) oligonucleotide dA6G10, which was previously shown to display a high affinity for the scavenger receptor A (SR-A). As compared to nontargeted virus, the linker protein equipped with bio-dA6G10 showed a 500-fold increased reporter gene expression in mouse macrophage RAW264.7 cells. A linker protein equipped with a bio-dA16 control oligonucleotide was inactive. Moreover, the bio-dA6G10-equipped linker showed a 390-fold increased luciferase expression in the macrophage cell line J774 and 276- and 150-fold increased reporter gene expression in primary peritoneal and bone marrow (BM)-derived macrophages, respectively. Using BM-derived macrophages from SR-A knockout mice, it was shown that the dA6G10-mediated uptake is predominantly SR-A-mediated. Thus, we have developed a novel tool to link biotinylated ligands to a virus-binding fragment of CAR and have exploi...Continue Reading

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Citations

Sep 25, 2010·Cancer Biotherapy & Radiopharmaceuticals·Fiorella PetronzelliRita De Santis
Nov 17, 2009·Molecular Immunology·Kok-Hooi YewChristopher Harrison
Nov 17, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ji Won ParkTae Gwan Park
Oct 22, 2008·Life Sciences·Yasuo YoshiokaShinsaku Nakagawa

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