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Near-infrared dual bioluminescence imaging in mouse models of cancer using infraluciferin

DOI: 10.7554/eLife.45801 DOI Help

Authors: Cassandra L. Stowe (University College London) , Thomas A. Burley (Institute of Cancer Research) , Helen Allan (University College London) , Maria Vinci (Institute of Cancer Research) , Gabriela Kramer-Marek (Institute of Cancer Research) , Daniela M Ciobota (Institute of Cancer Research) , Gary N. Parkinson (University of London) , Tara L. Southworth (Connecticut College) , Giulia Agliardi (University College London) , Alastair Hotblack (University College London) , Mark F. Lythgoe (University College London) , Bruce R. Branchini (Connecticut College) , Tammy L. Kalber (University College London) , James C Anderson (University College London) , Martin A. Pule (University College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Elife , VOL 8

State: Published (Approved)
Published: October 2019

Abstract: Bioluminescence imaging (BLI) is ubiquitous in scientific research for the sensitive tracking of biological processes in small animal models. However, due to the attenuation of visible light by tissue, and the limited set of near-infrared bioluminescent enzymes, BLI is largely restricted to monitoring single processes in vivo. Here we show, that by combining stabilised colour mutants of firefly luciferase (FLuc) with the luciferin (LH2) analogue infraluciferin (iLH2), near-infrared dual BLI can be achievedin vivo. The X-ray crystal structure of FLuc with a high-energy intermediate analogue, 5'-O-[N-(dehydroinfraluciferyl)sulfamoyl] adenosine (iDLSA) provides insight into the FLuc-iLH2 reaction leading to near-infrared light emission. The spectral characterisation and unmixing validation studies reported here established that iLH2 is superior to LH2 for the spectral unmixing of bioluminescent signals in vivo; which led to this novel near-infrared dual BLI system being applied to monitor both tumour burden and CAR T cell therapy within a systemically induced mouse tumour model.

Diamond Keywords: Enymes

Subject Areas: Biology and Bio-materials

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 30/10/2019 09:39

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Cancer Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)