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CMV enhancer may not be suitable for tissue-specific enhancement of promoters in cancer gene therapy

Cancer Gene Therapy volume 27, pages 389–392 (2020)Cite this article

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Gruh et al. [1] reported that when the human cytomegalovirus (CMV) immediate-early enhancer was integrated into lentiviral vectors before tissue or cell-specific promoters human atrial natriuretic factor (ANF), human ventricular myosin light chain (MLC2v), or type II alveolar epithelial cell (AT-2)-specific human surfactant protein C (SP-C), it could confer efficient cell-type-specific gene expression in cardiomyocytes, lung AT-2 cells, and nontarget cells. Based on their work, the authors claimed that lentiviral vectors containing the human CMV enhancer may be promising in gene therapy.

With great interest, we were attracted by this article which introduced a much more simple but potent transcriptional enhancement approach to overcome the low efficiency limitation of most tissue/cell-specific promoters used in current gene therapy vectors. We used an adenoviral vector, which infection is less selective, in our work of cancer gene therapy, and the expression of gene of interest must be restricted in cancer cells under the control of tumor-specific promoters to ensure the therapeutic efficacy and safety. We adopted the same sequence of the human CMV enhancer as reported by Gruh et al. [1] to enhance the transcription efficiency of two most widely used tumor-specific promoters, carcinoembryonic antigen (CEA) promoter, and alpha-fetoprotein (AFP) promoter. Luciferase reporter vectors were constructed in pGL4.10[luc2] and cotransfected with reference vector pGL4.74[hRluc/TK] into CEA and AFP positive carcinoma cells and negative control cells respectively, and the dual luciferase assay system was used to evaluate the transcription efficiency. Our results showed that the CMV enhancer not only greatly increased CEA or AFP promoter activity in CEA or AFP positive cells, but also significantly increased promoter activity in CEA or negative control cells, which means that CMV enhancer could not maintain the tumor-specific transcriptional activity of CEA or AFP promoter [2, 3].

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Acknowledgements

This work was supported by the Zhejiang Provincial Natural Science Foundation (No. LZ12H16003).

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  1. The authors contributed equally: Jing Jia, Shuzhi Zhang

Authors and Affiliations

  1. Institute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, China

    Zhenyu Jia & Shuzhi Zhang

  2. Center for Molecular Medicine, Zhejiang Academy of Medical Sciences, Hangzhou, China

    Jing Jia

  3. Clinical Research Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Jiang Cao

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Jia, Z., Jia, J., Zhang, S. et al. CMV enhancer may not be suitable for tissue-specific enhancement of promoters in cancer gene therapy. Cancer Gene Ther 27, 389–392 (2020). https://doi.org/10.1038/s41417-019-0106-x

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