AAV with ALB(1.9) promoter driven CreERT2

This AAV expresses CreERT2 driven by a liver ALB(1.9) promoter.

The ALB(1.9) is a synthetic promoter of ~1.9 Kb. It is based on the human Albumin promoter as well as several other regulatory elements. This synthetic promoter gives an extremely high level of long-term, liver-specific transgene expression that is 100-100 fold greater than that of the CMV promoter. For short-term (1-2 weeks post-injection into mouse liver), ALB(1.9) gives comparable expression relative to that of the CMV promoter. However, the expression level of the CMV promoter decreases 100-1000 fold from its peak level within 10-20 weeks of DNA administration whereas the ALB(1.9) promoter sustains its initial high level of expression for over 1 year. Compared to the regular ALB promoter, which is also commonly used for liver-specific transgene expression, the expression level from ALB(1.9) is about 10-100 fold greater.

A mutated form of estrogen ligand-binding domain (ERT2) that binds to synthetic antagonists (such as tamoxifen or its derivative 4-hydroxy-tamoxifen) but not to circulating estrogen, was fused to the Cre recombinase (Cre) to create CreERT2 (also known as “inducible Cre”). When tamoxifen binds to CreERT2, it induces a conformational change of CreERT2, leading to its nuclear translocation, followed by Cre/Lox-mediated recombination.