It is estimated that well over half a billion people worldwide are infected every year by pathogens transmitted by mosquito bites. Malaria and Dengue fever are two of the most debilitating mosquito-borne diseases, and many others wreak havoc throughout the world. Traditional approaches to mosquito control include the use of chemical sprays such as insecticides that contaminate crops, pollute waters and permeate the food chain with unexpected and unplanned off-target effects. In addition, mosquitoes can develop resistance to chemical sprays, thus greatly limiting their efficacy over time and further damaging the environment through increased use of these toxins.
The molecular mosquitocide (MM) program is a research effort in collaboration with faculty from Colorado State University (Barry Beaty) and Iowa State (Lyric Bartholomay) aimed at fundamentally changing how we control mosquito populations. By using the endogenous RNA interference (RNAi) pathway found throughout the animal kingdom, the goal of the MM program is to deliver RNA sequences via nanoparticles that target mosquito genes required for disease-transmission. Such RNA sequences may prevent mosquito reproduction or may impede mosquitoes from providing an environment suitable to host pathogens which cause human disease. These RNA sequences are both species and gene-specific, thus preventing resistance development and the panoply of off-target effects that current chemical spraying methods engender. Critically, nanoparticles shield RNA from rapid degradation and promote systemic biodistribution, two parameters integral to the eventual efficacy of the MM approach.
Initial studies are clarifying the role of size, shape and charge on the biodistribution of PRINT nanoparticles in Anopheles gambiae, the mosquito species which carries and transmits the causative agent of malaria (Figure 1). Using the inherent fabrication control of PRINT, these studies will help broaden our understanding of how particle parameters augment distribution throughout individual mosquito species at different stages of life (e.g., larvae and adults) with the aim of developing more tailored and efficacious molecular mosquitocides. For example, RNA sequences targeting mosquito genes involved in egg development will likely need to target the abdomen of adult mosquitoes, whereas targeting of the feeding cycle will require nanoparticles which can deliver RNA to the head of the mosquito. The molecular mosquitocide program combines the explosion of information accrued in mosquito genetics and genomics with the delivery capabilities of PRINT nanoparticles to provide an almost unlimited number of potential target genes and sequences for RNAi-based MMs.