Generation and selection of targeted adenoviruses embodying optimized vector properties.

The utility of adenovirus serotype 5 (Ad5)-based vectors for gene therapy applications would be improved by cell-specific targeting. However, strategies to redirect Ad5 vectors to alternate cellular receptors via replacement of the capsid fiber protein have often resulted in structurally unstable vectors. In view of this, we hypothesized that the selection of modified adenoviruses during their rescue and propagation would be a straightforward approach that guarantees the generation of functional, targeted vectors.

Genetic targeting strategies for adenovirus.

Adenovirus serotype 5 (Ad5) continues to be regarded as a gene delivery vehicle of high utility for a variety of clinical applications. However, targeting of the virus to alternate, non-native receptors has become a mandate for many gene therapy approaches, as inefficient viral transduction of target tissues has proven detrimental to the utility of Ad5. Thus, various targeting strategies have been endeavored to the end of highly specific cellular transduction, including that of genetic manipulation of the viral capsid.

A single-component CD40-targeted adenovirus vector displays highly efficient transduction and activation of dendritic cells in a human skin substrate system.

Dendritic cell (DC) based tumor vaccination usually involves the administration of ex vivo generated autologous DC. Transduction of DC by viral vectors in vivo has been proposed as a more standardized and easily clinically applicable approach. Previously, we have reported that an Ad5 vector targeted to CD40 via genetic capsid incorporation of CD40L achieves selective transduction of DC in vitro.