Manipulation of adenovirus interactions with host factors for gene therapy applications

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

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Publisher's URL: http://dx.doi.org/10.2217/nnm.11.186

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:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Baker, Professor Andrew and Duffy, Ms Margaret and Bradshaw, Dr Angela and Parker, Dr Alan
Authors: Duffy, M. R., Parker, A. L., Bradshaw, A. C., and Baker, A. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Centre for Population and Health Sciences
Journal Name:Nanomedicine
Publisher:Future Medicine
ISSN:1743-5889
ISSN (Online):1748-6963

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
519431Interrogation and manipulation of miRNA in acute vascular injuryAndrew BakerBritish Heart Foundation (BHF)RG/09/005/27915RI CARDIOVASCULAR & MEDICAL SCIENCES