siRNA-mediated targeting of the RNA-dependent RNA polymerase in the Norovirus genome

Human noroviruses are a major cause of epidemic and sporadic gastroenteritis worldwide and can chronically infect immunocompromised patients. Efforts to develop effective vaccines and antivirals have been hindered by the uncultivable nature and extreme genetic diversity of human noroviruses [1]. Previous therapies have focused on targeting nucleases and structural proteins. The norovirus RNA genome or viral transcripts also constitute an important target to inhibit the replication of norovirus. Finding a conserved component of the Norovirus genome would make it an ideal target that could overcome the genetic diversity of strains [2]. Gene-based therapy is the intentional modulation of gene expression in specific cells to treat pathological conditions. This modulation is accomplished by introducing exogenous nucleic acids such as small interfering RNA (siRNA). Given the large size and negative charge of this macromolecule, its delivery is typically mediated by carriers or vectors. Targeting the gastrointestinal (GI) tract represents a promising strategy for local or systemic delivery of gene-based therapeutics [3].