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KMID : 0613820210310111028
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Journal of Life Science
2021 Volume.31 No. 11 p.1028 ~ p.1036
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Study on the Safety of Firefly Luciferase in Human as a Transient Reporter Gene of Oncolytic Virotherapy
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Hong Young-Mi
Yoon Woong-Hee
Lee You-Ra
Kim Soo-Ji
Ngabire Daniel
Narayanasamy Badrinath
Ornella Mefotse Saha Cyrelle
Kim Myung-Hee
Cho Eun-A
Lee Bo-Ra
Hwang Tae-Ho
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Abstract
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Firefly luciferase (FLuc) can function as an efficient marker in the gene and viral therapies. Nonetheless, its clinical translation has been unaccomplished with the concerns on its exogenous nature and the similarity with human fatty acyl-CoA synthetase. In this study, we aimed to show safety of FLuc by conducting a set of preclinical experiments and a human use. Initially, FLuc permeability across the plasma membrane was investigated by delivering the FLuc-carrying viral vector, OTS-412, or the FLuc recombinant protein. After in vitro infection of OTS-412 into different cancer cell lines, FLuc activity was detected only in the cell lysates, but not in culture media. In addition, recombinant FLuc protein further showed the impermeability against the plasma membrane. Similar result was also observed in the in vivo experiment. After being injected into the VX2 tumor-bearing rabbit, the FLuc exclusively resided within the tumor tissue without being detected in the blood plasma or other organs. Human cancer cell lines originated from various organs were lysed and treated to the FLuc, and none of the human substrates was reactive against the FLuc. As a final step, FLuc recombinant protein was intravenously injected into a human. The luciferase was degraded with the half-life of 20 to 30 minutes in blood, and was untraceable from 1.5 hr after the injection. In addition, the blood plasma was nonresponsive against the fatty acids. Hematological analysis was also comparable between the pre- and post-injection. Altogether, our study collectively demonstrates the safety of the firefly luciferase.
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KEYWORD
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Firefly luciferase, human trial, oncolytic virus, OTS-412, reporter gene
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