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, Zhao Xiang Bian, William C.S. Tai, Ga Lai LawWing Tak Wong, Steven L. Cobb, Ka Leung Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

17 Citations (Scopus)

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

ASJC Scopus subject areas

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

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