Engineering synthetic medea-based and threshold- dependent underdominance-based gene drive systems in mosquitoes

Akbari, OM, J.; Antoshechkin, I.; Matzen, K.; Papathanos, P.; Kennedy, K.; Ward, C.; Chen, C. H.; Guo, M.; Hay, B.,  Pathogens and Global Health,  107:442-442. 2013.

Mosquito population replacement requires gene drive mechanisms in order to spread linked genes, mediating disease refractoriness, through wild populations. Medea is predicted to be a low threshold gene drive mechanism, able to spread from low initial frequency. Such a system is ideal when the goal is area-wide population replacement. However, once released, it is difficult to restore the pre-transgenic state, if desired. Drive mechanisms requiring that transgenes exceed a threshold frequency in order to spread provide an attractive alternative because they bring about local, but not global replacement, and transgenes can be eliminated through dilution of the population with wild-type individuals. Here we describe the first creation of a synthetic threshold-dependent gene drive system, designated maternal- effect lethal underdominance (UDMEL). We demonstrate threshold-dependent replacement in single- and two-locus configurations in Drosophila. We will describe the dynamics of the UDMEL system, and our progress in transferring Medea and UDMEL into Aedes aegypti.