By combining custom zinc finger (ZF) DNA-binding technology with protein fragment complementation, we have developed a technology, designated SEER (Sequence-Enabled Reassembly), that has the potential to "see" or detect genetic information within a living cell (Fig. 1). These agents consist of two inactive parts of signal-generating peptides that have the ability to recognize specific DNA sequences. The two parts bind near each other in the presence of a user-defined DNA target site and generate a fluorescent signal. Two prototype SEER systems have been constructed, based on the reassembly of green fluorescent protein (SEER-GFP) and the enzyme beta-lactamase (SEER-LAC). To our knowledge, these are the first examples of DNA-dependent reassembly of peptide fragments.
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