Normalizing the expression of an experimental reporter to the expression of a control reporter can help to differentiate specific from nonspecific effects of cell-treatment protocols. We have developed a luciferase-based technology, the Chroma-Luc™ Series Reporter Vectors. The Chroma-Luc™ Vectors include a vector encoding one red-emitting luciferase (CBRluc) and two vectors encoding green-emitting luciferases (CBG68lucand CBG99luc). The design of the synthetic Chroma-Luc™ genes is based on a native Yellow-Green luciferase gene originally cloned fromPyrophorus plagiophthalamus, a large click beetle indigenous to the Caribbean. To ensure reliability and high levels of expression, the Chroma-Luc™ genes have been codon optimized for mammalian expression and cleared of most known consensus transcription factor binding sites. In addition, the predicted peroxisome targeting sequences have been removed. Upon addition of the luciferase substrates, the engineered CBRlucluciferase emits red light (613nm), which has optimal color separation from the corresponding 537nm green-emitting Chroma-Luc™ luciferases (i.e., CBG68lucand CBG99luc).