Transgenic mosquito larvae, as shown by green fluorescence (top and bottom). Photo courtesy of Junitsu Ito et al. Nature © (2002) Macmillan Magazines Ltd.

Mosquito bites aren't just annoying: they are also often deadly, as mosquitoes are the obligate vectors for the malarial parasite Plasmodium. One way to reduce disease transmission by mosquito bites might be to genetically engineer the mosquitoes themselves, as a new study published by Junitsu Ito and colleagues in Nature suggests. Plasmodium enters the mosquito when it ingests an infected blood meal. It then proliferates in the midgut of the mosquito and is transmitted to a new host through another bite. After entering the host, the parasite must move through several mosquito epithelia to complete its development, thus providing a possible target to stop its deadly life cycle.

In previous work, the same lab identified a peptide that binds to mosquito epithelia. An excess of peptide can swamp out parasite–epithelial interactions, thus preventing the parasite from developing in the mosquito. The new work has taken this principle one step further with the creation of transgenic mosquitoes that express four linked copies of this peptide behind a signal peptide. Importantly, this multi-peptide protein is expressed from a promoter that is turned on in the midgut, specifically when the mosquito feeds on a blood meal. In this way, the peptide is expressed in the right place and at the right time to interfere with the parasite's life cycle. The transgenic mosquitoes (see accompanying picture) had a significantly lower susceptibility to parasite infection. Crucially, the authors then showed that parasite transmission levels were lowered by half in one transgenic line, and in two lines they were lowered to undetectable levels.

The possibility of stopping malarial transmission is an exciting one; however, as often with a milestone paper on a novel application, there are some problems to be surmounted. Plasmodium, like many organisms, has considerable genetic diversity and so might quickly develop resistance to the transgenic mosquitoes by using a different method to stay alive in the host. Thus, Ito et al. are continuing to look for additional genes that can be used in conjunction with the one encoding the peptide to completely stop transmission. The imminent publication of the genomes of both the parasite Plasmodium falciparum and the mosquito strain Anopheles gambiae should, of course, accelerate this research. However, even when mosquitoes are generated with several genetic modifications, there remain numerous problems with dispersing these mosquitoes in the field, and much thought will be needed before introducing these modifications into the environment. Yet, the prospect of preventing a disease that kills millions of humans every year is certainly strong motivation to explore all available options.