The pest control gene produces a protein called tTAV (tetracycline repressible activator variant), which is able to act as a switch to control the activity of other genes. It’s a variant because this gene has been optimised to only work in insect cells. In the modified insects, when the tTAV gene is expressed, the non toxic protein ties up the cell’s machinery so it’s other genes aren’t expressed and the insect dies. Because no toxic proteins are produced in the insects, if any animals eat them it would be the same as eating a wild insect – they will be digested in just the same way that all other insects are digested.
But how do we produce insects if they die? There’s an antidote given to the insects in the rearing facility that acts like a switch to turn off the tTAV gene preventing the tTA protein from working. This antidote, tetracycline, an antibiotic, binds to the tTAV protein and disables it. So in the presence of the antidote, the Oxitec insects are able to survive and reproduce in the rearing facility, but when the males are released into the wild, their offspring can’t access the antibiotic in the quantities needed to survive, so they die before reaching adulthood.
In diagram (a), the positive feedback system is composed of tetO21 (21 copies of a the tetracycline operator DNA sequence to which the tTAV protein binds in the absence of the tetracycline antidote) and a minimal promoter for switching on production of tTAV protein. b) Without the tetracycline antidote (repressor), the minimal promoter induces production of a small amount of tTAV, which then binds to the tetO21 binding sites. The binding of tTAV enhances expression of more tTAV, which in turn binds to more tetO21 sites and ties up the cell’s machinery so that the insects other genes aren’t expressed. This positive feedback loop results in the production of tTAV, which, at high enough levels, are deleterious to cells. (c) The tetracycline antidote binds to tTAV, changing its conformation, which prevents it from binding to tetO21. This turns off the positive feedback loop and only a basal amount of tTAV is produced, which is harmless to the cells in the presence of tetracycline.