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Molecular Targets for Therapy

A novel therapeutic molecule against HTLV-1 infection targeting provirus

Leukemia volume 27, pages 1621–1627 (2013)Cite this article

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Abstract

Human T-cell leukemia virus type 1 (HTLV-1), which causes adult T-cell leukemia (ATL) in humans, establishes a life-long latent infection. Current therapies are not very effective against HTLV-1-associated disorders. A novel therapeutic approach may help to combat HTLV-1 infection. A molecular therapy that targets the proviral genome is favorable because the therapeutic effect occurs specifically in HTLV-1-infected cells, regardless of whether they express viral genes. In this proof-of-concept study, we developed a therapeutic molecule based on zinc finger nuclease (ZFN) to achieve this goal. We designed a ZFN that specifically recognized conserved region of HTLV-1 long terminal repeat (LTR) and introduced it into various HTLV-1-positive human T-cell lines, including HTLV-1-transformed and ATL-derived cell lines. The ZFN disrupted the promoter function of HTLV-1 LTR and specifically killed HTLV-1-infected cells. We also showed a potential approach of this therapeutic molecule to remove the proviral genome from HTLV-1-infected cells, something that has not been possible before. The therapeutic effect of ZFN was confirmed in an in vivo model of ATL. This strategy may form the basis of a therapy that can eradicate HTLV-1 infection. Similar approaches can be used to target other malignancy-associated viruses.

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Acknowledgements

This work was supported by the Japan Health Science Foundation, the Japanese Ministry of Health, Labor and Welfare (H23-Shinko-Ippan-028).

Author contributions

AT, ST, EU, RK, KM, SO and JK planned and performed the experiments, and analyzed the data. AT, ST, SO and JK wrote the manuscript.

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Authors and Affiliations

  1. Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

    A Tanaka

  2. AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan

    S Takeda, E Urano & J Komano

  3. Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan

    R Kariya, K Matsuda & S Okada

  4. Department of Infectious Diseases, Division of Virology, Osaka Prefectural Institute of Public Health, Osaka, Japan

    J Komano

Authors
  1. A Tanaka
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  2. S Takeda
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  3. R Kariya
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  4. K Matsuda
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  5. E Urano
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  6. S Okada
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  7. J Komano
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Correspondence to J Komano.

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Tanaka, A., Takeda, S., Kariya, R. et al. A novel therapeutic molecule against HTLV-1 infection targeting provirus. Leukemia 27, 1621–1627 (2013). https://doi.org/10.1038/leu.2013.46

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