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Publication : An optimized bioluminescent substrate for non-invasive imaging in the brain.

First Author  Su Y Year  2023
Journal  Nat Chem Biol Volume  19
Issue  6 Pages  731-739
PubMed ID  36759751 Mgi Jnum  J:341257
Mgi Id  MGI:7536891 Doi  10.1038/s41589-023-01265-x
Citation  Su Y, et al. (2023) An optimized bioluminescent substrate for non-invasive imaging in the brain. Nat Chem Biol 19(6):731-739
abstractText  Bioluminescence imaging (BLI) allows non-invasive visualization of cells and biochemical events in vivo and thus has become an indispensable technique in biomedical research. However, BLI in the central nervous system remains challenging because luciferases show relatively poor performance in the brain with existing substrates. Here, we report the discovery of a NanoLuc substrate with improved brain performance, cephalofurimazine (CFz). CFz paired with Antares luciferase produces greater than 20-fold more signal from the brain than the standard combination of D-luciferin with firefly luciferase. At standard doses, Antares-CFz matches AkaLuc-AkaLumine/TokeOni in brightness, while occasional higher dosing of CFz can be performed to obtain threefold more signal. CFz should allow the growing number of NanoLuc-based indicators to be applied to the brain with high sensitivity. Using CFz, we achieve video-rate non-invasive imaging of Antares in brains of freely moving mice and demonstrate non-invasive calcium imaging of sensory-evoked activity in genetically defined neurons.
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