Date Published: February 10, 2009
Publisher: Public Library of Science
Author(s): John M Marshall, Charles E Taylor
Abstract: John Marshall and Charles Taylor review recent advances in the development of transgenic mosquitoes for malaria control.
Partial Text: Malaria has been eliminated from a large part of the world. By the mid-twentieth century both North America and Europe were free of the disease, although both had suffered greatly during the prior century [1,2]. While a variety of means were used to achieve this eradication, the most important are thought to be reducing the number of breeding sites for malaria vectors and improving residential areas to separate humans from mosquitoes.
Malaria in humans results from infection by any of five species of Plasmodium: P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. These are transmitted to humans by approximately 50 species of mosquitoes, all belonging to the genus Anopheles. In sub-Saharan Africa, the vast majority of deaths are caused by P. falciparum transmitted by An. gambiae and the closely related An. arabiensis. These species are difficult to work with in the laboratory, so other model systems of malaria are often used in laboratory studies.
More problematic is the means of driving a refractory construct quickly and efficiently through the vector mosquito population so that the population of susceptible mosquitoes will be replaced. Transposable elements (TEs) were one of the first gene drive systems to gain widespread attention for population replacement . These elements are able to spread quickly through a population due to their ability to replicate within a host genome and hence to be inherited more frequently in the offspring’s genome. This increase in inheritance enables TEs to spread even in the presence of a fitness cost to the host . It has also led to their widespread prevalence among many taxa, to the extent that various families of TEs represent 47% of the Aedes aegypti mosquito genome .
The first requirement of any transgenic mosquito project will be the discovery of genes that confer resistance to human vector-borne diseases. The proof of principle has been shown for rodent and chicken malaria, and it remains to optimize genes to confer resistance to human malaria. Several refractory genes will be necessary for a successful intervention both to improve the efficacy of refractoriness, and to reduce the probability that resistance to antipathogen genes will emerge in the Plasmodium population.
Malaria control with transgenic mosquitoes will be challenging; however, recent advances suggest that it may be a possibility in the foreseeable future. Progress towards discovering refractory genes for rodent malaria and gene drive systems for Drosophila provide hope that similar advances may be made for human malaria in mosquito vector species.