RNA Interference for Mosquito and Mosquito-Borne Disease Control

Abstract

RNA interference (RNAi) is a powerful tool to silence endogenous mosquito and mosquito-borne pathogen genes in vivo. As the number of studies utilizing RNAi in basic research grows, so too does the arsenal of physiological targets that can be developed into products that interrupt mosquito life cycles and behaviors and, thereby, relieve the burden of mosquitoes on human health and well-being. As this technology becomes more viable for use in beneficial and pest insect management in agricultural settings, it is exciting to consider its role in public health entomology. Existing and burgeoning strategies for insecticide delivery could be adapted to function as RNAi trigger delivery systems and thereby expedite transformation of RNAi from the lab to the field for mosquito control. Taken together, development of RNAi-based vector and pathogen management techniques & strategies are within reach. That said, tools for successful RNAi design, studies exploring RNAi in the context of vector control, and studies demonstrating field efficacy of RNAi trigger delivery have yet to be honed and/or developed for mosquito control.

Keywords: Aedes aegypti; Anopheles gambiae; RNA interference; RNAi; mosquito control; vector control.

Figure 1

Mosquito life cycle events in the context of RNAi interventions (see also Table 1). Key life stage events illustrated in the context of targeted RNAi in mosquito disease vectors (1–8). Existing frameworks for mosquito control are shown in the context of mosquito life events to highlight points where RNAi triggers can be delivered. Control measures for particular life stages include: (A) Attractive Toxic Sugar Bait (ATSB); (B) residual spray & Long Lasting Insecticidal Bed-nets (LLIN); (C) Attractive Baited Oviposition Trap (ABOT); and (D) larvicides and pupacides. All of these control measures are at risk of resistance development (red arrows). Numerals in the figure correspond to Section 2 of the text and Table 1.

Figure 2

Diverse examples of mosquito RNAi trigger delivery systems (see also Table 2). The variety of (A) delivery vehicles and (B) RNAi trigger producing nucleic acids employed to suppress genes in mosquito species. Examples shown include: (1) naked RNAi triggers such as dsRNA, siRNA, or chemically modified siRNA (star shape); (2) transfection agents with dsRNA or shRNA expressing plasmids; (3) nanoparticles of abiotic or biotic origin in combination with dsRNA or plasmids; (4) viral expression systems carrying dsRNA or ssRNA that is converted to dsRNA in the cell; (5) bacterial expression systems containing dsRNA or shRNA plasmids; and (6) yeast expression systems containing dsRNA or shRNA plasmids. Numerals in the figure correspond to Section 3 of the text and Table 2.