Scientists at The Pirbright Institute have created flightless mosquitoes by editing a specific gene that is required for females to fly. This could provide a more controlled and targeted way of reducing mosquito populations (females bite to obtain a blood meal and thereby spread disease; males do not bite) in select areas where mosquito-borne diseases such as Zika and dengue are rife.
Insecticides such as pyrethroids have been used for over four decades in attempts to reduce the burden of mosquito-borne diseases, which cause over one million deaths every year. However, resistance to these chemicals is starting to appear and their broad action on other insects pose a threat to local ecosystems. Developing smarter, more specific tools using genetic engineering to prevent the transmission of mosquito-borne diseases therefore presents a potential solution.
Studies published in PLOS Neglected Tropical Diseases describe how Pirbright researchers recognised that a unique genetic trait in the flight muscles of mosquitoes provides a potential target for use in gene drives – a genetic method that ensures a desired characteristic is inherited at a higher than normal rate, enabling its spread through a population.
The mosquitoes Aedes aegypti and Culex quinquefasciatus, which transmit diseases like dengue, Zika, and West Nile fever, have an unusual characteristic in that some of the fundamental genes involved in flight are different in males and females. The Pirbright researchers targeted Act4, the gene responsible for producing a protein called actin in female mosquitoes’ flight muscles, which is essential for muscle function.
By editing Act4 female mosquitoes were unable to produce functioning actin proteins, resulting in defective flight muscles. This rendered them incapable of flying, whilst their male counterparts were unaffected since they use a different gene for their actin.
This discovery has great potential for future use in genetic population control methods. As engineered males are unaffected, they would theoretically be just as fit as their wild counterparts, meaning they would be able to compete for female mates with equal efficiency, ensuring the engineered Act4 gene is inherited and resulting in female offspring that would be unable to fly.
Without flight, females are unable to mate and find a human to feed on their blood. This would prevent females that inherit the edited Act4 gene from feeding on humans and transmitting diseases as well as stopping them from producing offspring, therefore reducing the population if enough females inherit the gene. The late acting nature of this trait would enable offspring to compete with wild populations during their larval stages, which would prevent wild mosquitoes from taking their place and result in an even greater population reduction.
Professor Luke Alphey, head of Arthropod Genetics at Pirbright said: “Our work emphasises the importance of obtaining a thorough understanding of mosquito biology and investigating differences between male and female genetics and physiology. There has been good progress investigating female fertility genes, but the unique control of actin production in females provides a different pathway for population control strategies to pursue. This is a positive step towards providing new tools to tackle diseases like dengue, Zika and West Nile fever, although further work is needed to assess the mating competitiveness of the engineered males and their compatibility with gene drive systems.”
Notes to editors
This study was funded by the Wellcome Trust Collaborative Award, the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation (UKRI), MRC Case studentship and NERC iCASE studentship.
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About The Pirbright Institute
The Pirbright Institute is a world leading centre of excellence in research and surveillance of virus diseases of farm animals and viruses that spread from animals to humans. Based in the UK and receiving strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC) part of UK Research and Innovation (UKRI), the Institute works to enhance capability to contain, control and eliminate these economically and medically important diseases through highly innovative fundamental and applied bioscience.
The Institute is an independent company, limited by guarantee and a registered charity, governed by a Board of non-executive Trustee Directors.
With an annual income of £35 million from grants and commercial activity, and a total of £25.2 million strategic investment from BBSRC UKRI during 2019-2020, the Institute contributes to global food security and health, improving quality of life for animals and people.
For more information about The Pirbright Institute see: www.pirbright.ac.uk
About BBSRC UKRI
The Biotechnology and Biological Sciences Research Council (BBSRC) is part of UK Research and Innovation (UKRI), a non-departmental public body funded by a grant-in-aid from the UK government.
BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.
Funded by government, BBSRC invested £451 million in world-class bioscience in 2019-20.
We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.
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