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Biosensor development

A chemical solution for FRET(ful) pairs

Nature Chemical Biology volume 19, pages 1048–1049 (2023)Cite this article

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The development of biosensors has been slowed by the optimization required for each new iteration. Now, the ChemoX platform facilitates the expansion of sensor design, resulting in unique Förster resonance energy transfer pairings with versatile applications and optimized readouts.

In this issue of Nature Chemical Biology, Hellweg et al.7 describe ChemoX, a new platform that enables the design of sensors with near-quantitative FRET ratios and clearer analyte-dependent readouts. This modular platform provides straightforward expansion of color palettes into the far red region, variable fluorescence lifetimes, incorporation of bioluminescence and the ability to multiplex (Fig. 1b). At its core, ChemoX uses a type of pairing that optimizes FRET between a genetically encoded donor fluorescent protein (such as enhanced green fluorescent protein (eGFP) or mRuby2) and a cell-permeable synthetic fluorophore acceptor that self-assembles with an encoded HaloTag7 protein8. The scaffold that surrounds the ChemoX pairing was developed to produce a near one-to-one FRET transfer by minimizing the distance between the fluorescent protein donor and the acceptor dye, and stabilizing the pair to decrease entropy within the system. ChemoX requires the use of only one synthetic fluorophore but benefits from the variety of modern readily interchangeable HaloTag7-compatible dyes9 (Fig. 1b (i)). Additionally, these dyes can be selected to have minimal background overlap with the fluorescent protein donor.

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Fig. 1: Comparison of a conventional approach and the ChemoX platform.

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  1. Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA

    Scott N. Lyons & Xiaolu A. Cambronne

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  1. Scott N. Lyons
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  2. Xiaolu A. Cambronne
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Correspondence to Xiaolu A. Cambronne.

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Lyons, S.N., Cambronne, X.A. A chemical solution for FRET(ful) pairs. Nat Chem Biol 19, 1048–1049 (2023). https://doi.org/10.1038/s41589-023-01403-5

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