The WPRE improves genetic engineering with site-specific nucleases

Inclusion of the woodchuck hepatitis virus post-transcriptional response element (WPRE) in the 3’ UTR of mRNA encoding zinc-finger or TALE nucleases results in up to a fifty-fold increase in nuclease expression and a several-fold increase in nuclease-modified chromosomes. Significantly, this increase is additive with the enhancement generated by transient hypothermic shock. The WPRE-mediated improvement is seen across several types of human and mouse primary and transformed cells and is translatable in vivo to the mouse liver.