Can we make friendly mosquitoes?May 8, 2019
Any organism, when challenged by any other, will try to protect itself. This is the natural order of self-preservation. Therefore, mosquitoes also have a natural mechanism to fight Plasmodium by being refractory to the infection. This fundamental biological aspect has been exploited to eliminate malaria, potentially making friendly mosquitoes (Ferreira MU et al. Clin Diag Lab Immunol 2004;11(6):987-95). There can be different strategies to make the vector plasmodium-resistant, the first approach is to replace the existing parasite-carrying mosquitoes with modified mosquitoes, the second is driven by an artificial gene, and the third by using modified microorganisms as delivery systems. The common step in all these methods is to use an effector molecule or gene to cause refractiveness to Plasmodium. An ideal effector would not modify the viability of the vector but target the parasite at different stages. Some of the interesting effectors identified so far include salivary gland and midgut peptide 1 (SM1), which blocks recognition sites for sporozoites and ookinetes (Ito J et al. Nature 2002, 417(6887):452-5) and the other one is phospholipase A2 (PLA2), which inhibits ookinete invasion (Zieler H et al. J Exp Biol 2001;204:4157-67).
The idea of replacing wild-type mosquitoes with a genetically modified one with a killing or disabling agent will usually need an intensive insect elimination in a given area. Apart from that, due to the unknown nature of genetic modifications that happen in modified mosquitoes, periodic and sustained release mechanisms will be needed. These steps make it highly costly and difficult to sustainably achieve targets. The gene-driven method, which aims at reducing one sex of insects to crush the population, uses transposable elements called “selfish genes” that use host DNA repair mechanism to develop the refractory system. Similar experiments were published with synthetic genetic elements and a homing endonuclease gene (HEG) called I-SceI, where it was demonstrated that the progeny of Anopheles gambiae can propagate genetic modifications.
Successful, large-scale implementations of transmission blocking methodologies for malaria elimination are still further away in the future. However, several unique technologies are being developed with a lot of focus, generating a huge amount of knowledge. Better data collection and qualitative analysis of randomized clusters, with well-defined endpoints, should be the main objective of studies now. The ideal endpoint should be the reduction of human infection and to help in taking informed and early clinical decisions. Any approach involving genetic modifications will need a well-planned compartmental and mechanistic mathematical modeling for better outcomes. Furthermore, any technology developed must have long-term benefits with low costs for affordable mass implementation even in remote regions.
Last, but among the most important considerations, are ethical development and the use of technologies for benefiting the patients. Education and population sensitization prior to implementation, touching upon the considerable epidemiological effects of releasing modified mosquitoes, are needed to really understand if we can make friendly mosquitoes.