Only a handful of tagged molecules have been used successfully in vivo to monitor gene expression. The most commonly used are β-galactosidase (β-gal) and green fluorescent protein (GFP). Both molecules pose limitations with in vivo detection. When using GFP, autofluorescence may be encountered in tissues and tissue sections. Similarly, when using β-gal as a marker, the penetration of X-gal substrate is difficult in tissues with extensive extra cellular matrix and in calcified tissues.