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EBNA1-targeted probe for the imaging and growth inhibition of tumours associated with the Epstein–Barr virus

Jiang, L.; Lan, R.; Huang, T.; Chan, C.; Li, H.; Lear, S.; Zong, J.; Wong, W.; Lee, M.M.; Chan, B.D.; Chan, W.; Lo, W.; Mak, N.; Lung, M.L.; Tsao, S.W.; Taylor, G.S.; Bian, Z.; Tai, W.C.S.; Law, G.; Wong, W.T.; Cobb, S.L.; Wong, K.L.

EBNA1-targeted probe for the imaging and growth inhibition of tumours associated with the Epstein–Barr virus Thumbnail


Authors

L. Jiang

R. Lan

T. Huang

C. Chan

H. Li

S. Lear

J. Zong

W. Wong

M.M. Lee

B.D. Chan

W. Chan

W. Lo

N. Mak

M.L. Lung

S.W. Tsao

G.S. Taylor

Z. Bian

W.C.S. Tai

G. Law

W.T. Wong

K.L. Wong



Abstract

Epstein–Barr nuclear antigen 1 (EBNA1), a dimeric oncoprotein of the Epstein–Barr virus (EBV), is essential for both viral-genome maintenance and the survival of infected cells. Despite EBNA1’s potential as a therapeutic target, tools for the direct monitoring of EBNA1 in vitro and in vivo are lacking. Here, we show that a peptide-based inhibitor that luminesces when bound to EBNA1 inside the nucleus of EBV+ cells can regulate EBNA1 homodimer formation and selectively inhibit the growth of EBV+ tumours of nasopharyngeal carcinoma cells (C666-1 and NPC43) and Burkitt’s lymphoma Raji cells. We also show that the peptide-based probe leads to 93% growth inhibition of EBV+ tumours in mice. Our findings support the hypothesis that selective inhibition of EBNA1 dimerization can be used to afford better EBV-related cancer differentiation, and highlight the potential application of the probe as a new generation of biotracers for investigating the fundamental biological function of EBNA1 and for exploring its application as a therapeutic target.

Citation

Jiang, L., Lan, R., Huang, T., Chan, C., Li, H., Lear, S., …Wong, K. (2017). EBNA1-targeted probe for the imaging and growth inhibition of tumours associated with the Epstein–Barr virus. Nature Biomedical Engineering, 1, Article 0042. https://doi.org/10.1038/s41551-017-0042

Journal Article Type Article
Acceptance Date Jan 31, 2017
Online Publication Date Mar 13, 2017
Publication Date Mar 13, 2017
Deposit Date Jun 14, 2016
Publicly Available Date Jan 26, 2021
Journal Nature biomedical engineering.
Print ISSN 2157-846X
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 1
Article Number 0042
DOI https://doi.org/10.1038/s41551-017-0042

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