Bioluminescent reporters used in laboratories are mostly derivatives of two major luciferase families: ATP-dependent insect luciferases and ATP-independent marine luciferases. Despite that ATP-dependent luciferase-luciferin pairs, such as firefly luciferase (FLuc)-D-luciferin, have been widely used for in vivo bioluminescence imaging (BLI), they consume ATP for photon production and this metabolic disruption issue cannot be addressed by simply improving these reporters. Moreover, any bioluminescent biosensors derived from them are intrinsically ATP-dependent. On the other hand, ATP-independent marine luciferase-luciferin pairs, such as NanoLuc-furimazine have found broad applications in vitro, but they are far from optimal for in vivo BLI due to low photon penetration depth in tissue caused by their blue emission, poor substrate solubility and stability, and/or low substrate permeability through the blood-brain barrier (BBB). In this talk, I will discuss our recent progress in integrating synthetic/medicinal chemistry, protein engineering, and in vivo validation to enhance ATP-independent luciferases for in vivo BLI.

ATP-independent bioluminescent reporters for <i>in vivo </i> imaging

2019 Fall National Meeting

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ATP-independent bioluminescent reporters for in vivo imaging