期刊
NANOMEDICINE
卷 7, 期 2, 页码 271-288出版社
FUTURE MEDICINE LTD
DOI: 10.2217/NNM.11.186
关键词
adenovirus; blood; factor X; gene therapy; hexon hypervariable regions; intravascular; liver
资金
- Scottish Universities Life Sciences Alliance
- British Heart Foundation
- British Heart Foundation [RG/09/005/27915] Funding Source: researchfish
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.
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