Gene Drive Systems for Controlling Mosquitoes

Stephanie Richards, PhD, Medical Entomologist

Mosquitoes that are immune to infection by pathogens…is that possible and do we want that to happen? If we can’t rid the world of mosquitoes, can we at least render them harmless (aside from the itchy welt that female mosquitoes leave when they blood feed on us)? These are some questions faced by scientists tasked with protecting public health by helping control potentially dangerous mosquito populations.

What are gene drive systems?

CRISPR (clustered regularly interspaced palindromic repeats) and Cas (genes associated with CRISPR) components are involved in the immune system of many bacteria in nature. Within the last five years, scientists have used this knowledge to craft genetic engineering tools, such as the CRISPR/Cas9 gene editing system. An enzyme is used by CRISPR to cut a portion of DNA and insert another sequence of code (designed by a scientist, in this case).

The development of gene drive systems may help propagate these genetic modifications in wild mosquito populations at a faster rate (essentially all progeny are affected) than natural inheritance between generations, hence potentially driving mosquitoes to become resistant to pathogens over subsequent generations.

Since it only takes approximately one week (depending on environmental conditions) for a mosquito egg to become an adult mosquito (after going through larval and pupal stages), advancements in gene drive systems have the potential for major impact on mosquito populations.

What are the practical applications for gene editing and gene drive systems?

This technology can potentially render female mosquitoes resistant to infection with pathogens (e.g., viruses [diseases such as dengue and Zika], protozoans [diseases such as malaria]) by identifying and destroying foreign DNA or RNA. Even without gene editing/gene drive, not all mosquitoes are competent vectors for all pathogens and this “vector competence” depends on a variety of biological and environmental factors.

Some scientists are also studying how gene drive systems can make female mosquitoes (Anopheles gambiae – primary vector of the malaria protozoan) sterile, hence this could be a method for suppressing mosquito populations and would, in this case, be self-limiting in nature. Other scientists think the CRISPER/Cas9 and gene drive technology could be used to genetically modify mosquitoes so that only (harmless) male mosquitoes are produced.

Other scientists think the CRISPER/Cas9 and gene drive technology could be used to genetically modify mosquitoes so that only (harmless) male mosquitoes are produced.

Can genetically modified mosquitoes compete with wild mosquitoes?

In order for any genetically modified mosquitoes to compete with wild mosquito populations, the modified mosquitoes must have the same level of fitness and fertility as wild mosquitoes. The “anti-pathogen genes” (in mosquitoes having this genetic modification) would also need to be tightly linked to the gene drive system so the positive effects are not lost in offspring from genetically modified mosquitoes mating with wild mosquitoes.

Ideally, gene drive systems would be useful for many mosquito species and populations against a variety of pathogens, e.g. Aedes aegypti and chikungunya/dengue/Zika viruses; Anopheles gambiae and malaria protozoan parasite. There may be a need to change more than one gene in a mosquito in order to achieve the desired effect.

Scientists would also need to consider (even if unlikely) and determine if a mosquito’s resistance to one pathogen (facilitated by genetic modification) might facilitate their ability to transmit a different pathogen. It will be important for scientists to challenge genetically modified mosquitoes to a variety of different pathogens (different genotypes of the same pathogen, as well as different types of pathogens) as part of the evaluation process.

Other Genetically Modified Mosquito Technologies

Others have already developed self-limiting genetically modified mosquitoes (Aedes aegypti (primary vector of chikungunya, dengue, and Zika viruses) that, when released and mate with wild mosquitoes, cause the resulting offspring to die. Some field trials have already been conducted using this technology outside of the United States. However, this technology does not have a gene drive component, hence for this type of genetically modified mosquito, large numbers of mosquitoes need to be released repeatedly.

How well will gene drive systems work in nature?

In some cases, errors in gene editing can be made that help prevent the code from continuing. In nature, there is no guarantee that the genetic changes put forth by scientists to help reduce vector effectiveness, reproduction or other aspects of mosquito biology will continue in perpetuity.

Will gene editing and gene drive systems replace traditional methods for integrated mosquito management?

Scientists continue to study this technology and how it can be used to help reduce vector borne disease and protect public health. As insecticide resistance continues to be an issue for controlling mosquitoes, new tools must be developed for mosquito control. While it remains important to manage insecticide resistance, in part, by conducting surveillance-based targeted control, genetically modified mosquitoes may be a tool that can be used in the future as part of a well-rounded integrated mosquito management program. This is especially important in areas where vector borne disease poses a significant threat to public health.

References

Adelman Z, Tu T (2016) Control of mosquito-borne infectious diseases: Sex and gene drive. Cell Press 32:219-229.

Callaway E (2017) Gene drives thwarted by emergence of resistant organisms. Nature 542: 15.

Hammond A, Galizi R, Kyrou K, Simoni A, Siniscalchi C, Katsanos D, Gribble M, Baker D, Marois E, Russell S, Burt A, Windbichler N, Crisanti A, Nolan T (2016) CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nature Biotechnology 34:78-83.

 

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