[Malaria: from genetic and molecular biology to disease control]

Abstract

The knowledge of the genomic structure of Plasmodium falciparum and of its main vector, Anopheles gambiae, may offer new perspectives for malaria therapy, vaccines or control of mosquito-borne transmission. New targets for future antimalarial drugs were identified, mainly apicoplast (a vestige of a vegetal structure incorporated by the parasite) and several enzymes, particularly proteases. The practical difficulty is now to select a few number of these "promising molecules", probably no more than 3 or 4, for a preclinical and clinical pharmaceutical development. Indeed, several other antimalarial drugs are already under development, and the industrial possibilities for developing new drugs are evidently limited. Many new vaccination targets and antigenic proteins were also identified. According to scientific and industrial limitations, a complete evaluation of these antigens is absolutely necessary to select a few of them for clinical development. For anti-malarial vaccinations, DNA vaccines may offer the most interesting perspectives, with the possibility of simultaneous immunisation against different Plasmodium stages and of an adjuvant effect by adding a gene encoding certain cytokines. In Anopheles gambiae genome, several genes encoding key-proteins (particularly odorant receptors necessary for blood feeding) were identified, as other genes encoding for proteins limiting the sexual development of Plasmodium inside its vector. From a theoretical viewpoint, genetically modified non biting or non transmitting mosquitoes offer new perspectives for the control of malaria transmission, but until now, the preliminary practical attempts gave rather poor results. On the whole, the genomic and proteomic of Plasmodium falciparum and Anopheles gambiae yielded exciting scientific results, but it is still too early and very speculative to imagine their practical applications for the control of malaria.