Department of Biology
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.
Source Publication Title
Nature Biomedical Engineering
Link to Publisher's Edition
Jiang, L., Lan, R., Huang, T., Chan, C., Li, H., Lear, S., Zong, J., Wong, W., Lee, M., Chan, B., Chan, W., Lo, W., Mak, N., Lung, M., Lung, H., Tsao, S., Taylor, G., Bian, Z., Tai, W., Law, G., Wong, W., Cobb, 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. https://doi.org/10.1038/s41551-017-0042