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

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Authors

  • 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
  • Zhao Xiang Bian
  • William C.S. Tai
  • Ga Lai Law
  • Wing Tak Wong
  • Steven L. Cobb
  • Ka Leung Wong

Colleges, School and Institutes

External organisations

  • Hong Kong Baptist University
  • Hong Kong Polytechnic University
  • Durham University
  • University of Hong Kong

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.

Details

Original languageEnglish
Article number0042
JournalNature Biomedical Engineering
Volume1
Issue number4
Publication statusPublished - 13 Mar 2017