Sterile Male

As a first stage in the development of our technologies, we have produced a sterile male Anopheles gambiae mosquito. The sterile males can mate with wild females, but the mating does not result in any offspring.

To create these sterile males, we are using a nuclease gene that, when activated during sperm production, fragments the X chromosome of the sperm and of the egg upon fertilisation, resulting in no offspring. As there are no offspring, the modification cannot be passed on to future generations of mosquitoes.

The primary purpose of this first stage is for our teams to acquire knowledge and build operational capacity. This stage also allows us to start a conversation with our local stakeholders in the communities where we conduct project activities, as well as with national and international stakeholders.

What’s a sterile male?

  • Target Malaria researchers have developed male mosquitoes carrying a modification that causes them to be sterile. These mosquitoes produce no offspring when mating with a wild female mosquito.
  • Modified Male + Wild Female produce no offspring.
  • The sex of a malaria mosquito is determined by the sex chromosomes, X and Y. Like in humans, female mosquitoes have two X chromosomes and male mosquitoes have an X and a Y chromosome.
  • Wild Male and Wild Female Illustration
  • Female mosquitoes only produce eggs with an X chromosome. Male mosquitoes produce sperm with either an X or a Y chromosome. For this reason, it is sperm from the male that ultimately determines the sex of the mosquito offspring.
  • Wild Male and Wild Female Illustration
  • There are unique sites on the X chromosome that are not found on any other chromosome in the malaria mosquito.
  • Unique Site Injections
  • Target Malaria researchers have modified a naturally occurring nuclease gene that produces a nuclease enzyme which recognises these sites and cuts through them, leaving the X chromosome fragmented and non-functional.
  • Nuclease Gene and Enzyme being cut into chromosome
  • This gene is activated only in males, and only during sperm production.
  • Modified Female and Wild Male Inheritance Diagram
  • The nuclease destroys the X chromosome in the sperm, and destroys the X chromosome in the egg upon fertilisation. This means modified males produce no progeny.
  • Because they produce no offspring, the sterile male mosquitoes cannot pass on their genes and quickly disappear from the environment.
  • Modified Male and Wild Female produce no offpspring. Wild Male and Wild Female produce offspring
  • The purpose of this stage, is for our teams to acquire knowledge and build capacity, and allow us to start a conversation with our stakeholders.
  • Target Malaria researcher sharing information

Our development pathway

Our project employs a phased development pathway, following the recommendations made by several expert groups, including the 2014 World Health Organisation (WHO) Guidance framework for testing of genetically modified mosquitoes, the 2016 National Academies of Sciences, Engineering and Medicine report Gene Drives on the Horizon and most recently, the 2018 Pathway to Implementation of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group,.

For the sterile male mosquito, we first developed our modified strain under contained laboratory conditions at Imperial College London (discovery), then we assessed the modified mosquitoes (strain characterisation studies in small and large cages) and gathered the data to submit a regulatory dossier. Small cage studies were conducted at Imperial College London and the large cage studies at the University of Perugia and Polo GGB, Italy. The regulatory dossier is submitted to the relevant authorities of the country of the partner institution that will carry out the research. The dossier goes through a thorough review by the relevant national authorities of that country, which decides whether to allow the next phase of the research to proceed. If the decision is positive, then the project imports the modified mosquitoes to the institution’s laboratory where it will be studied further under containment.

These studies in country will then gather further data to include in other regulatory submission(s) to the national regulatory authorities to ask for a permit to conduct the next stage of our research, a small-scale release study.

All the results of the stages of the first phase of our research will be used to inform and develop our subsequent phases: the male-bias self-limiting and our gene drive approaches.

Stakeholder engagement

Throughout each phase, we carry out stakeholder engagement activities, to ensure that communities participating or directly affected by the research can make an informed decision about project activities and that these decisions are recorded. Our engagement goes beyond what is required by law because we see engagement as a process that helps us improve our research.

All the entomological studies that are carried out in the field sites throughout the project are accompanied by engagement activities. Individual consent is required before we are able to carry out mosquito collections in homes or compounds, and village level acceptance is needed for other collection methods, such as larval sites sampling and swarming.

Before mosquitoes are brought in for work under containment, the project engages with communities around the institution’s insectary to explain our work and what the work under containment will entail. When communities around the insectaries feel they have been informed and their questions have been adequately addressed, the project then asks them to make a collective decision about whether to allow the work under containment to proceed.

In all the sites, our stakeholder engagement team organises group meetings, village or neighbourhood-wide activities and other approaches to ensure residents are informed and have the opportunity to feedback and discuss. We have also put in place a grievance mechanism at each site, which allows residents to register any complaint anonymously. Finally, to ensure that when the stakeholder engagement team is not onsite residents can still access information, there are local ‘relay’ teams in the villages, who live onsite and are a resource for the residents.

Go to Phase 2

Self Limiting