Both the MS2 and MB systems are capable of imaging single RNA transcripts in living cells. Nonetheless, the MS2 system has been used more widely, despite the fact that MBs offer several advantages including smaller probe size, versatility in fluorophore/quencher selection, improved signal-to-background due to quenching, and the ability to image endogenous RNAs (Table 1). One major obstacle that hampers the widespread use of MBs is their tendency to be sequestered into the nucleus where they can generate FPSs as a result of nonspecific protein binding and/or nuclease degradation , , , , , .