Adenoviral Vector Targeting via Mitigation of Liver Sequestration

Only a few diseases can be addressed by delivering genes or vectors to a single tissue. In many cases, systemic delivery by intravenous injection will be the best approach to deliver therapeutic viruses throughout the body. Although the intravenous route is appealing, adenoviruses are bound and sequestered by an overlapping arsenal of antipathogen elements that inactivate or mistarget these therapeutics. These include interactions with natural antibodies, adaptive antibodies, blood factors, complement, blood cells, endothelial cells, Kupffer cells, macrophages, and liver hepatocytes. Many of these interactions occur by binding to the 720 copies of the hexon protein that is a multivalent patterned surface on adenovirus icosahedrons. We describe here our current understanding of interactions with the adenovirus hexon and methods to avoid loss of viruses during systemic therapy.