In the second phase of our project, we will study a self-limiting male bias strain. This consists of modified males which are fertile but produce predominantly male offspring. We have produced a self-limiting male bias mosquito strain by using a nuclease gene that, when activated during sperm production, fragments the X chromosome of the sperm, resulting in a mosquito that mainly has Y-bearing sperm and thus produces predominantly male offspring.
This phase is very similar to one of our final technologies but without a gene drive. This means that the modification is passed on only for a certain number of generations. This is possible by inserting the nuclease gene into a mosquito’s autosome. An autosome is any chromosome that is not a sex chromosome. Anopheles gambiae mosquitoes have two pairs of autosomes and one pair of sex chromosomes. Each autosome in a pair is inherited 50% of the time and will be inherited by 50% of the offspring.
The purpose of this phase is to better inform the development pathway of our final technologies and to strengthen and widen our stakeholder engagement using a self-limiting fertile male modified mosquito, that will decline in number at each generation.
What’s a self-limiting male bias mosquito?
Our development pathway
Progress on the self-limiting male bias is promising, however it is still under development. The development pathway for the self-limiting male bias mosquito would be very similar to the pathway of the sterile male. We first develop our modified strain under contained laboratory conditions in London (discovery), then we assess the modified strain (strain characterisation studies) and gather the necessary data to submit a regulatory dossier to the relevant authority of the country of the partner institution we are working with. The regulatory dossier then goes through a thorough review, this is done by the relevant national authorities of that country and will then inform Target Malaria of its decision. If the decision is positive, then the project moves on to import its strain to the partner institution’s contained laboratory where it will be studied further. These studies will gather the necessary data to submit a dossier to the regulatory authority of the country to ask for a permit to conduct a small-scale release study. The authorities that grants the permission are the regulatory and national authorities of the country.
The results of our second phase will help inform the further development of our mosquito reduction technologies.
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
The activities we carry out for the self-limiting male bias strain will be similar to the ones described for PHASE 1. The phased approach allows us to build knowledge and understanding with the communities around the insectaries and in the field sites, so the engagement for this second phase will be a continuation of the engagement for the first phase.