Towards Covalent Fluorescent Light-Up Aptamers (coFLAPs)

Abstract

The fluorogen-activating aptamer, Spinach, was a milestone in cellular RNA imaging and conceptually similar to the green fluorescent protein (GFP). Since then, more than ten FLAP systems have been developed across a broad spectral range. All of these systems differ fundamentally from GFP in that FLAPs rely on noncovalent fluorogen–RNA interactions, whereas GFP integrates its fluorophore covalently. In this article, we discuss recently developed FLAPs, including the first covalent FLAP, coPepper, as a promising new strategy to overcome current limitations in FLAP-based RNA imaging. Moreover, the bioconjugation chemistry developed for coFLAPs has immediate impact on covalent RNA labeling, RNA drug targeting, and in general, on covalent drug design.