Review
doi: 10.1038/s41579-018-0025-0.
Controlling vector-borne diseases by releasing modified mosquitoes
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- PMID: 29777177
- PMCID: PMC7612058
- DOI: 10.1038/s41579-018-0025-0
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Review
Controlling vector-borne diseases by releasing modified mosquitoes
Heather A Flores et al.
Nat Rev Microbiol.
2018 Aug.
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Abstract
Aedes mosquito-transmitted diseases, such as dengue, Zika and chikungunya, are becoming major global health emergencies while old threats, such as yellow fever, are re-emerging. Traditional control methods, which have focused on reducing mosquito populations through the application of insecticides or preventing breeding through removal of larval habitat, are largely ineffective, as evidenced by the increasing global disease burden. Here, we review novel mosquito population reduction and population modification approaches with a focus on control methods based on the release of mosquitoes, including the release of Wolbachia-infected mosquitoes and strategies to genetically modify the vector, that are currently under development and have the potential to contribute to a reversal of the current alarming disease trends.
Conflict of interest statement
Heather A. Flores and Scott L. O’Neill work for The World Mosquito Program.
Figures
Evidence consensus map showing the complete absence to complete presence of dengue. Green colours indicate evidence consensus towards absence of dengue, and orange and red colours indicate consensus towards presence of dengue. Darker colouring indicates more data supporting a conclusion about the presence or absence of dengue in a country. Figure adapted from ref .
New vector control approaches that involve the release of mosquitoes aim to reduce the vector population. A) In the sterile insect technique (SIT) approach, male insects are exposed to either irradiation or sterilizing chemicals, causing large-scale random damage to the insect chromosomes or dominant-lethal mutations in the sperm. These males are then released in the wild population, and when they mate with wild females, viable offspring are rarely produced, eventually leading to a substantial decrease in vector population size. B) In the incompatible insect technique approach, a Wolbachia strain is stably introduced into a colony of a mosquito species. Only Wolbachia-infected males are released, which when mated to females that do not harbour the same Wolbachia strain or that do not carry Wolbachia, results in the death of their offspring due to CI. A combination of IIT and SIT could be used to suppress mosquito populations. During this approach, Wolbachia-infected mosquitoes are treated with low level irradiation. As in IIT alone, Wolbachia-males mating with wild females will not produce offspring. In the case of accidental female releases, these irradiated females are sterile and cannot reproduce with wild or Wolbachia-infected males. C) RIDL (Release of Insects carrying a Dominant Lethal) is a suppression strategy, whereby males that carry a transgene that causes late-acting lethality are released in the open field. These males mate with wild-type females, and the resulting offspring die before reaching the pupal stage.
A) Using Wolbachia in the incompatible insect technique (IIT) approach, results in population reduction. In IIT, a Wolbachia strain is stably introduced into a colony of a mosquito species. Only Wolbachia-infected males are released, which when mated to females that do not harbour the same Wolbachia strain or that do not carry Wolbachia, results in the death of their offspring due to CI. Large numbers of males are released to increase the number of incompatible matings that are occurring. Over time, the population of disease-competent mosquitoes will decrease. B) Wolbachia can also be used to modify a mosquito population. Both Wolbachia-infected male and female mosquitoes are generally released over a 12-16 week period. CI provides a reproductive advantage to Wolbachia-infected females resulting in the spread and establishment of Wolbachia in the population. These Wolbachia-infected females are resistant to arboviruses such as dengue, Zika, and chikungunya.
A) Homing endonuclease genes (HEGs) encode endonuclease genes that recognize a specific DNA sequence and catalyse a break, which is then naturally repaired through homology-directed repair resulting in non-Mendelian inheritance. B) The CRISPR-Cas9 system is analogous to HEGs; however, a guide RNA (gRNA) provides sequence specificity for DNA cleavage by the Cas9 nuclease which is then repaired through homology-directed repair. Examples of CRISPR-Cas9 used in population modification and reduction approaches include C) the addition of vector competence genes with the Cas9-gRNA construct resulting in virus-resistant offspring , D) creating a gRNA to targeting female fertility genes resulting in sterile females , and creating a gRNA to target X-chromosome-specific sequences resulting in a reduction of female offspring . The Cas9-gRNA constructs inherited by any surviving offspring resulting in its continual spread.
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