Disruption of dengue virus transmission by mosquitoes

• DENV2 resistance in transgenic mosquitoes overexpressing an antiviral IR effector.
• Design of a hammerhead ribozyme that efficiently blocks DENV2 in cell culture.
• Trans-splicing Group I Intron blocking all four DENV serotypes in cell culture.

Current control efforts for mosquito-borne arboviruses focus on mosquito control involving insecticide applications, which are becoming increasingly ineffective and unsustainable in urban areas. Mosquito population replacement is an alternative arbovirus control concept aiming at replacing virus-competent vector populations with laboratory-engineered incompetent vectors. A prerequisite for this strategy is the design of robust anti-pathogen effectors that can ultimately be genetically driven through a wild-type population. Several anti-pathogen effector concepts have been developed that target the RNA genomes of arboviruses such as dengue virus in a highly sequence-specific manner. Design principles are based on long inverted-repeat RNA triggered RNA interference, catalytic hammerhead ribozymes, and trans-splicing Group I Introns that are able to induce apoptosis in virus-infected cells following splicing with target viral RNA.