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Manipulation of adenovirus interactions with host factors for gene therapy applications

Duffy, Margaret R., Parker, Alan L., Bradshaw, Angela C. and Baker, Andrew H. 2012. Manipulation of adenovirus interactions with host factors for gene therapy applications. Nanomedicine 7 (2) , pp. 271-288. 10.2217/nnm.11.186

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Abstract

Nanomedicine based on the use of adenovirus vectors for therapeutic gene delivery shows broad potential. Specific targeting for many gene therapy applications, such as metastatic cancers or cardiovascular diseases requires intravascular delivery of the vector. However, a major barrier to successful adenovirus vector targeting follows systemic delivery, as upon contact with the bloodstream the virus interacts with a variety of host proteins, in particular coagulation factor X, which mediates profound liver gene transfer. This inherent hepatic tropism combined with macrophage scavenging minimizes the efficacy of the virus at the desired sites and induces toxic side effects. Understanding the complex, multifaceted interactions of adenovirus with host factors is of vital importance to the design of safer vectors with improved efficacy and pharmacokinetic profiles. Increased knowledge of adenovirus biology provides the opportunity to develop innovative strategies to detarget the virus from the liver following intravascular delivery and redirect the vector to disease areas.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RM Therapeutics. Pharmacology
Publisher: Future Medicine
ISSN: 1743-5889
Last Modified: 04 Jun 2017 04:42
URI: http://orca.cf.ac.uk/id/eprint/43281

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