• The potential for harm to humans via horizontal gene transfer (HGT) was investigated as part of a risk assessment of a proposed field release of genetically modified mosquitoes of the Anopheles gambiae s.s species complex. • The genomes of humans and Anopheles gambiae s.s and Anopholes coluzzii mosquitoes were assessed for evidence of historical HGT events. All regions of substantial similarity could be explained by conventional conservation through inheritance. • Additional pathways to harm via the disruption of the human genome through the integration of genetic modifications were explored, including the potential for the transcription and disruption of endogenous functions, with no additional risks identified. Genetic biocontrol is a novel strategy that may one day be used to combat the spread of invasive species and infectious diseases. A comprehensive assessment of potential ecological and human health risks was recently completed for a proposed field study of Anopheles coluzzii mosquitoes genetically modified to carry a paternal male bias (PMB) construct. This genetic strain is an interim product on a development pathway towards a cost-effective genetic control strategy for malaria in sub-Saharan Africa. As part of this analysis, we investigated the potential for the PMB construct to be transferred from mosquitoes to humans via horizontal gene transfer (HGT) after limited field release. A comprehensive genetic analysis searched for evidence of historical HGT events between humans and mosquitoes in the Anopheles gambiae s.s complex and assessed the potential for the PMB construct to integrate into the human genome. Of the 5,462 regions identified as similar between the human and mosquito genomes, 4,697 were explainable via conventional inheritance, 536 lacked characteristics indicative of HGT, and the final 229 could be explained via expected sequence variations. Hence, no evidence of historical HGT events between mosquitoes and humans was identified. Similarly, analyses of the construct sequence revealed none of the indicators that would suggest likely alternate pathways of integration or transcription, indicating no evidence for a pathway to harm humans via the HGT of the PMB construct. Bioinformatic risk assessments such as these will be important for the development and regulation of future genetic biocontrol strategies.
Wickramarachchi et al. (Wed,) studied this question.