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 Law; Wing Tak Wong; Steven L. Cobb; Ka-Leung Wong

doi:10.1038/s41551-017-0042

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 Law^*Wing Tak Wong^*, Steven L. Cobb^*, Ka-Leung Wong^*

^*Corresponding author for this work

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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 language	English
Article number	0042
Journal	Nature Biomedical Engineering
Volume	1
Issue number	4
Early online date	13 Mar 2017
DOIs	https://doi.org/10.1038/s41551-017-0042
Publication status	Published - Apr 2017

Scopus Subject Areas

Biotechnology
Bioengineering
Medicine (miscellaneous)
Biomedical Engineering
Computer Science Applications

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Jiang, L., Lan, R., Huang, T., Chan, C. F., Li, H., Lear, S., Zong, J., Wong, W. Y., Muk-Lan Lee, M., Dow Chan, B., Chan, W. L., Lo, W. S., Mak, N. K., Li Lung, M., Lung, H. L., Wah Tsao, S., Taylor, G. S., Bian, Z., Tai, W. C. S., ... Wong, K-L. (2017). EBNA1-targeted probe for the imaging and growth inhibition of tumours associated with the Epstein-Barr virus. Nature Biomedical Engineering, 1(4), [0042]. https://doi.org/10.1038/s41551-017-0042

@article{58f3eb5151244390b9221cf6ffc2df86,

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

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.",

author = "Lijun Jiang and Rongfeng Lan and Tao Huang and Chan, {Chi Fai} and Hongguang Li and Sam Lear and Jingyi Zong and Wong, {Wing Yan} and {Muk-Lan Lee}, Magnolia and {Dow Chan}, Brandon and Chan, {Wai Lun} and Lo, {Wai Sum} and Mak, {Nai Ki} and {Li Lung}, Maria and Lung, {Hong Lok} and {Wah Tsao}, Sai and Taylor, {Graham S.} and Zhaoxiang Bian and Tai, {William C S} and Law, {Ga Lai} and Wong, {Wing Tak} and Cobb, {Steven L.} and Ka-Leung Wong",

note = "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).",

year = "2017",

month = apr,

doi = "10.1038/s41551-017-0042",

language = "English",

volume = "1",

journal = "Nature Biomedical Engineering",

issn = "2157-846X",

publisher = "Nature Publishing Group",

number = "4",

}

Jiang, L, Lan, R, Huang, T, Chan, CF, Li, H, Lear, S, Zong, J, Wong, WY, Muk-Lan Lee, M, Dow Chan, B, Chan, WL, Lo, WS, Mak, NK, Li Lung, M, Lung, HL, Wah Tsao, S, Taylor, GS, Bian, Z, Tai, WCS, Law, GL, Wong, WT, Cobb, SL & Wong, K-L 2017, 'EBNA1-targeted probe for the imaging and growth inhibition of tumours associated with the Epstein-Barr virus', Nature Biomedical Engineering, vol. 1, no. 4, 0042. https://doi.org/10.1038/s41551-017-0042

TY - JOUR

T1 - EBNA1-targeted probe for the imaging and growth inhibition of tumours associated with the Epstein-Barr virus

AU - Jiang, Lijun

AU - Lan, Rongfeng

AU - Huang, Tao

AU - Chan, Chi Fai

AU - Li, Hongguang

AU - Lear, Sam

AU - Zong, Jingyi

AU - Wong, Wing Yan

AU - Muk-Lan Lee, Magnolia

AU - Dow Chan, Brandon

AU - Chan, Wai Lun

AU - Lo, Wai Sum

AU - Mak, Nai Ki

AU - Li Lung, Maria

AU - Lung, Hong Lok

AU - Wah Tsao, Sai

AU - Taylor, Graham S.

AU - Bian, Zhaoxiang

AU - Tai, William C S

AU - Law, Ga Lai

AU - Wong, Wing Tak

AU - Cobb, Steven L.

AU - Wong, Ka-Leung

N1 - 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).

PY - 2017/4

Y1 - 2017/4

N2 - 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.

AB - 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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U2 - 10.1038/s41551-017-0042

DO - 10.1038/s41551-017-0042

M3 - Article

AN - SCOPUS:85029945130

SN - 2157-846X

VL - 1

JO - Nature Biomedical Engineering

JF - Nature Biomedical Engineering

IS - 4

M1 - 0042

ER -

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

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