Adenovirus – a blueprint for gene delivery

Abstract

A central quest in gene therapy and vaccination is to achieve effective and long-lasting gene expression at minimal dosage. Adenovirus vectors are widely used therapeutics and safely deliver genes into many cell types. Adenoviruses evolved to use elaborate trafficking and particle deconstruction processes, and efficient gene expression and progeny formation. Here, we discuss recent insights into how human adenoviruses deliver their double-stranded DNA genome into cell nuclei, and effect lytic cell killing, non-lytic persistent infection or vector gene expression. The mechanisms underlying adenovirus entry, uncoating, nuclear transport and gene expression provide a blueprint for the emerging field of synthetic virology, where artificial virus-like particles are evolved to deliver therapeutic payload into human cells without viral proteins and genomes.