Abstract
Polyomaviruses are small icosahedral dsDNA viruses that have been widely investigated as potential gene delivery vectors in the last two decades. Polyomavirus capsid proteins, when produced in heterologous expression systems, self-assemble into virus like particles (VLPs).
These VLPs can be loaded with various clinically relevant cargos to serve as vehicles for the intracellular delivery of genes, proteins or chemical compounds. Due to the absence of pre- existing immunity against mouse polyomavirus (MPyV) in the human population, we investigated MPyV as a potential gene and drug delivery vector for anticancer therapy.
Similarly to the wild type virus, MPyV vectors readily enter target cells through the binding of sialic acid, but the efficiency of gene expression by transduced genes is rather low. We identified the restricted capacity of MPyV vectors to escape from the endocytic system as a major bottleneck for their application as gene delivery systems.
Here we present data demonstrating that gene transduction efficacy of MPyV vectors can be facilitated by cationic polymers (polyethylenimine) and also, in contrast to the adenovirus vector, by histidine rich peptides. Furthermore, we present the concept of the MPyV vector design that can be applied for cancer cell targeting and cargo release into the cytosol.