Molecular biology

RIDL genetic constructs include conditional, dominant lethal mutations.

Different molecular constructs are used in the different products to achieve the desired target profiles. One version includes an elegant positive feedback system in which no specific effectors are needed to cause death.

In diagram (a), the positive feedback system is composed of a tetO binding domain, a minimal promoter and the tTA gene. Without the repressor (b), the minimal promoter induces production of a small amount of tTA, which then binds to the tetO binding sites.  The binding of tTA enhances expression of more tTA, which in turn binds to more tetO sites. This positive feedback loop results in the production of tTA, which, at high enough levels, are deleterious to cells. (c) The repressor is able to bind to tTA and block it from binding to tetO, turning off the positive feedback loop and only a basal amount of tTA is produced, which is harmless to the cells.

 

 

 

 

 

 

 

 

For more information read Fu et al Nature Biotech; Gong et al 2005 Nature Biotech.