Gene drive: Harnessing gene editing advances for Anopheline gene drive

About

In recent years gene drive technology became extremely relevant and timely, especially given the promising potential to be used to control mosquito vectors of diseases. For the first time, in 2018 a gene drive mosquito strain has been engineered to suppress populations of human malaria mosquitos in small lab cages without developing resistance (Nature Biotechnology, volume 36). However, these initial proofs of concept may not be sufficiently robust to achieve regulatory approval and field impact. Even if they do, resistance in some form is likely to arise eventually, and subsequent-generation gene drive products will be desirable to improve performance and/or combat resistance.

Polo GGB has recently been awarded funds by the Gates Foundation to carry out the project ‘Gene drive: Harnessing gene editing advances for Anopheline gene drive’. This investment will fund a leading gene editing group at Polo GGB to continue to work with Anopheline gene drive developers to advance gene editing techniques. Together with Polo GGB, the group includes the Crisanti Lab at Imperial College London and Keith Joung’s group at Massachusetts General Hospital.

The project is focused on both translating new advances from gene editing and other fields to gene drive technology and being responsive to any issues identified with first-generation gene drive products. This translates into three main outcomes: i) the use of state-of-the-art detection methods to evaluate off-target CRISPR cleavage and to evaluate the impact of natural polymorphism in target site specificity; ii) to identify novel and/or improved nucleases that have optimum efficiency for mosquito physiological temperature for future gene drive or gene editing applications and iii) to develop proof-of-principle designs of self-limiting drives using preferential recombination and reprogrammable modules.

Specifically, Polo GGB’s contribution is focused on the identification of novel nucleases, by exploring CRISPR systems from mosquito microbiota. This will expand the molecular repertoire for mosquito gene drive systems and will impact other fields as well.