Hi, mammalian cells do not have endogenous luciferase activity, and normally luminescence background is low. So your luminescence signal should be relatively specific. Hence your control should be more based on your biological response consideration, such as effects of transfection reagents on cells, DNA/RNA toxicities, etc. I would suggest use a mock vector, or a vector with a non-targeting DNA sequence, with the same transfection procedures to your targeted samples.