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Abstract:
The idea of introducing genetic modifications into wild populations of insects to stop them from spreading diseases is more
than 40 years old. Synthetic disease refractory genes have been successfully generated for mosquito vectors of dengue
fever and human malaria. Equally important is the development of population transformation systems to drive and maintain
disease refractory genes at high frequency in populations. We demonstrate an underdominant population transformation
system in Drosophila melanogaster that has the property of being both spatially self-limiting and reversible to the original
genetic state. Both population transformation and its reversal can be largely achieved within as few as 5 generations. The
described genetic construct {Ud} is composed of two genes; (1) a UAS-RpL14.dsRNA targeting RNAi to a haploinsufficient
gene RpL14 and (2) an RNAi insensitive RpL14 rescue. In this proof-of-principle system the UAS-RpL14.dsRNA knock-down
gene is placed under the control of an Actin5c-GAL4 driver located on a different chromosome to the {Ud} insert. This
configuration would not be effective in wild populations without incorporating the Actin5c-GAL4 driver as part of the {Ud}
construct (or replacing the UAS promoter with an appropriate direct promoter). It is however anticipated that the approach
that underlies this underdominant system could potentially be applied to a number of species.
