Genetic approaches for malaria control

The already unacceptable large burden of malaria continues to increase, indicating that the available means to fight the disease are insufficient. The genetic manipulation of the mosquito vectorial competence is a potential new promising weapon for the control of malaria. Considerable progress has been made in recent years towards this goal. It is now possible to introduce synthetic genes into the mosquito germ line, promoters have been identified that effectively drive gene expression in tissues and at times appropriate to target the parasite, and effector genes that impair parasite development in the mosquito have been identified. With these tools, proof-of-concept experiments have already demonstrated that it is possible to interfere genetically with the vectorial competence of the mosquito. At least some of the transgenic mosquito lines that have been created appear to be as fit as their wild-type counterparts. Presently, the major unresolved challenge is the development of methods to drive effector genes into mosquito populations in the field. While several approaches are under consideration, such as transposable elements, Wolbachia, meiotic drive and paratransgenesis, their relative feasibility remains to be demonstrated. Additional challenges are the resolution of safety concerns and satisfactorily addressing social, ethical and political considerations. Hopes remain high that the remaining challenges will be solved and that we shall be able to deploy this new genetic weapon in the foreseeable future.