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Malaria

Ending Malaria

Organisms: The related malarial mosquitoes An. gambiae s.s., An. coluzzi, An. arabiensis.

Laboratories: Catteruccia (Harvard School of Public Health), Church (Harvard Medical School), Esvelt (MIT). We are also discussing potential collaborations with the team at Imperial College London (Burt, Crisanti, Windbichler) who are exploring different approaches.

Safeguards: Always employed: ecological confinement (not native to the Boston area), barrier confinement (at least 6 locked doors including two equipped with air curtains).

Rationale:
In the last three minutes, over a thousand people were infected with malaria. Two of them – most likely children under the age of 5 – will die. The rest will suffer from fevers and debilitating weakness. Eradicating malaria would likely do more for human well-being and economic development than any other infectious disease. This is why GiveWell has listed the Against Malaria Foundation as one of their top-rated charities per dollar donated since 2009. While a gene drive approach would not be a silver bullet, it could be effective enough to permit eradication.

Experimental Plan:
We are building gene drive cassettes designed to spread through wild populations of 3 of the 4 primary mosquito vectors of malaria in Africa. Our approach specifically targets and recodes two essential genes, one of them likely to be haploinsufficient, inserting the gene drive cassette in the middle. By using multiple guide RNAs targeting each gene, the resulting drive system should prevent the emergence of drive-resistant alleles, which would require mutations in all target sites that do not disrupt either gene. This generic cassette could be used as a chassis for numerous types of antimalarial gene drive systems.