Capsid modification strategies for detargeting adenoviral vectors

Parker, A. L., Bradshaw, A. C. , Alba, R., Nicklin, S. A. and Baker, A. H. (2013) Capsid modification strategies for detargeting adenoviral vectors. In: Chillon, M. and Bosch, A. (eds.) Adenovirus: Methods and Protocols [3rd.]. Series: Methods in molecular biology (1089). Humana Press, pp. 45-59. ISBN 9781627036788 (doi: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 Sections
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Nicklin, Professor Stuart and Bradshaw, Dr Angela and Baker, Professor Andrew and Parker, Dr Alan and Alba, Dr Raul
Authors: Parker, A. L., Bradshaw, A. C., Alba, R., Nicklin, S. A., and Baker, A. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Publisher:Humana Press
ISSN:1064-3745
ISBN:9781627036788

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