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Capsid modification strategies for detargeting adenoviral vectors

Parker, Alan L., Bradshaw, Angela C., Alba, Raul, Nicklin, Stuart A. and Baker, Andrew H. 2013. Capsid modification strategies for detargeting adenoviral vectors. In: Chillon, Miguel and Bosch, Assumpcio eds. Adenovirus, Vol. 1089. Methods in Molecular Biology, Humana Press, pp. 45-59. (10.1007/978-1-62703-679-5_3)

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Abstract

Adenoviral vectors hold immense potential for a wide variety of gene therapy based applications; however, their efficacy and toxicity is dictated by “off target” interactions that preclude cell specific targeting to sites of disease. A number of “off target” interactions have been described in the literature that occur between the three major capsid proteins (hexon, penton, and fiber) and components of the circulatory system, including cells such as erythrocytes, white blood cells, and platelets, as well as circulatory proteins including complement proteins, coagulation factors, von Willebrand Factor, p-selectin as well as neutralizing antibodies. Thus, to improve efficacious targeting to sites of disease and limit nonspecific uptake of virus to non-target tissues, specifically the liver and the spleen, it is necessary to develop suitable strategies for genetically modifying the capsid proteins to preclude these interactions. To this end we have developed versatile systems based on homologous recombination for modification of each of the major capsid proteins, which are described herein.

Item Type: Book Section
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Adenovirus; Replication deficient; Gene therapy; Hexon; Penton base; Fiber; Capsid modification; Homologous recombination
Publisher: Humana Press
ISBN: 978-1-62703-678-8
Last Modified: 04 Jun 2017 08:51
URI: http://orca.cf.ac.uk/id/eprint/86540

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