Codon-Optimized Luciferase Variants for Mammalian Gene Expression in Culture and in Vivo

Luciferases have proven to be useful tools in advancing our understanding of biologic processes. Having a multitude of bioluminescent reporters with different properties is highly desirable. We characterized codon-optimized thermostable green- and red-emitting luciferase variants from the Italian fi...

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Main Authors: Casey A. Maguire, Johannes C. van der Mijn, Marja H. Degeling, Danielle Morse, Bakhos A. Tannous
Format: Article
Language:English
Published: SAGE Publishing 2012-01-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2011.00022
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author Casey A. Maguire
Johannes C. van der Mijn
Marja H. Degeling
Danielle Morse
Bakhos A. Tannous
author_facet Casey A. Maguire
Johannes C. van der Mijn
Marja H. Degeling
Danielle Morse
Bakhos A. Tannous
author_sort Casey A. Maguire
collection DOAJ
description Luciferases have proven to be useful tools in advancing our understanding of biologic processes. Having a multitude of bioluminescent reporters with different properties is highly desirable. We characterized codon-optimized thermostable green- and red-emitting luciferase variants from the Italian firefly Luciola italica for mammalian gene expression in culture and in vivo. Using lentivirus vectors to deliver and stably express these luciferases in mammalian cells, we showed that both variants displayed similar levels of activity and protein half-lives as well as similar light emission kinetics and higher stability compared to the North American firefly luciferase. Further, we characterized the red-shifted variant for in vivo bioluminescence imaging. Intramuscular injection of tumor cells stably expressing this variant into nude mice yielded a robust luciferase activity. Light emission peaked at 10 minutes post-D-luciferin injection and retained > 60% of signal at 1 hour. Similarly, luciferase activity from intracranially injected glioma cells expressing the red-shifted variant was readily detected and used as a marker to monitor tumor growth over time. Overall, our characterization of these codon-optimized luciferases lays the groundwork for their further use as bioluminescent reporters in mammalian cells.
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spelling doaj-art-3e21215b046944be810bd86f0d92d9f52025-01-02T02:58:00ZengSAGE PublishingMolecular Imaging1536-01212012-01-011110.2310/7290.2011.0002210.2310_7290.2011.00022Codon-Optimized Luciferase Variants for Mammalian Gene Expression in Culture and in VivoCasey A. MaguireJohannes C. van der MijnMarja H. DegelingDanielle MorseBakhos A. TannousLuciferases have proven to be useful tools in advancing our understanding of biologic processes. Having a multitude of bioluminescent reporters with different properties is highly desirable. We characterized codon-optimized thermostable green- and red-emitting luciferase variants from the Italian firefly Luciola italica for mammalian gene expression in culture and in vivo. Using lentivirus vectors to deliver and stably express these luciferases in mammalian cells, we showed that both variants displayed similar levels of activity and protein half-lives as well as similar light emission kinetics and higher stability compared to the North American firefly luciferase. Further, we characterized the red-shifted variant for in vivo bioluminescence imaging. Intramuscular injection of tumor cells stably expressing this variant into nude mice yielded a robust luciferase activity. Light emission peaked at 10 minutes post-D-luciferin injection and retained > 60% of signal at 1 hour. Similarly, luciferase activity from intracranially injected glioma cells expressing the red-shifted variant was readily detected and used as a marker to monitor tumor growth over time. Overall, our characterization of these codon-optimized luciferases lays the groundwork for their further use as bioluminescent reporters in mammalian cells.https://doi.org/10.2310/7290.2011.00022
spellingShingle Casey A. Maguire
Johannes C. van der Mijn
Marja H. Degeling
Danielle Morse
Bakhos A. Tannous
Codon-Optimized Luciferase Variants for Mammalian Gene Expression in Culture and in Vivo
Molecular Imaging
title Codon-Optimized Luciferase Variants for Mammalian Gene Expression in Culture and in Vivo
title_full Codon-Optimized Luciferase Variants for Mammalian Gene Expression in Culture and in Vivo
title_fullStr Codon-Optimized Luciferase Variants for Mammalian Gene Expression in Culture and in Vivo
title_full_unstemmed Codon-Optimized Luciferase Variants for Mammalian Gene Expression in Culture and in Vivo
title_short Codon-Optimized Luciferase Variants for Mammalian Gene Expression in Culture and in Vivo
title_sort codon optimized luciferase variants for mammalian gene expression in culture and in vivo
url https://doi.org/10.2310/7290.2011.00022
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AT marjahdegeling codonoptimizedluciferasevariantsformammaliangeneexpressionincultureandinvivo
AT daniellemorse codonoptimizedluciferasevariantsformammaliangeneexpressionincultureandinvivo
AT bakhosatannous codonoptimizedluciferasevariantsformammaliangeneexpressionincultureandinvivo