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.
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This work is funded by the Hong Kong Baptist University (FRG2/14-15/013013), Hong Kong Polytechnic University (HKPolyU), Hong Kong Research Grants Council (HKBU 20301615), Hong Kong Polytechnic University Central Research Grant (G-UC08), Hong Kong Research Grants Council (PolyU 153012/15P), University Research Facility for Chemical and Environmental Analysis (UCEA) and Area of Excellent Grants (1-ZVGG) of Hong Kong Polytechnic University, ECS-Grant - RGC (PolyU 253002/14P), HK PolyU (PolyU 5096/13P), HKBU and HKPolyU Joint Research Programme (RC-ICRS/15-16/02F-WKL02F-WKL), the EPSRC (Durham University, DTA award) and Research Grants Council of the Hong Kong SAR for the NPC Area of Excellence (AoE/M 06/08 Center for Nasopharyngeal Carcinoma Research).
The authors declare no competing financial interests.
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Jiang, L., Lan, R., Huang, T. et al. EBNA1-targeted probe for the imaging and growth inhibition of tumours associated with the Epstein–Barr virus. Nat Biomed Eng 1, 0042 (2017). https://doi.org/10.1038/s41551-017-0042
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