Applying synthetic biology to the development of in vivo technologies for the monitoring and control of vector-borne diseases

The ability to genetically modify insects of medical and agricultural importance has opened up the potential for intentionally introducing genetic traits into insect populations. This can be done to alter their ability to reproduce, cause crop damage, or transmit disease-causing pathogens. However, there are challenges in getting the introduced traits to spread throughout the population. Usually, the added genetic trait does not improve the fitness of the insects carrying it, and sometimes it even has a negative effect. This means that a large number of modified insects, often tens of millions, need to be released to have a significant impact on the population. This process is costly and logistically challenging, and the effects only last as long as the continuous release of large numbers of modified insects.
Recent advancements in genetic control, such as “gene drive,” address this problem by biasing the inheritance of the modification in each generation. This means that the frequency of the modified trait can increase rapidly in the population. These approaches show promise because they are self-sustaining, requiring only a few released insects to have a long-term effect, and they are species-specific since the modified traits are passed on through mating between insects of the same species. Many gene drive designs utilize genome editing tools like CRISPR to bias the inheritance of the gene drive element in sperm or eggs, which are then passed on to the next generation. By making small changes to the CRISPR element, such as its duration and timing of DNA cleavage activity, its performance in terms of inheritance can be drastically affected. Limiting the expression of the gene drive element to the germline cells, where it needs to be active, can greatly enhance the fitness of insects carrying the gene drive and increase its chances of spreading through the target population. Additionally, many gene drives contain a genetic “cargo” that produces a desired effect in the insects carrying it, such as activating the immune system against a pathogen or interfering with parasite replication. Expressing these effects only in non-infected insects or specific tissues can be costly. Having the ability to fine-tune the expression of the gene drive and its cargo within the insect, both in terms of timing and location, can significantly improve their effectiveness by effectively minimising expression of the different elements to only the cells or conditions where it is essential that they act.

Project Details

Genetics and Genomics
Vector Control

Feb 2024 — Mar 2027

$2.16M

United Kingdom