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

Lijun Jiang, Rongfeng Lan, Tao Huang, Chi Fai Chan, Hongguang Li, Sam Lear, Jingyi Zong, Wing Yan Wong, Magnolia Muk-Lan Lee, Brandon Dow Chan, Wai Lun Chan, Wai Sum Lo, Nai Ki MAK, Maria Li Lung, Hong Lok LUNG, Sai Wah Tsao, Graham S. Taylor, Zhaoxiang BIAN, William C S TAI, Ga Lai LawWing Tak Wong, Steven L. Cobb, Ka-Leung WONG

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16 Citations (Scopus)
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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.

Original languageEnglish
Article number0042
JournalNature Biomedical Engineering
Volume1
Issue number4
DOIs
Publication statusPublished - 10 Apr 2017

Scopus Subject Areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

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