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Gene Therapy and Immunosenescence

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Handbook of Immunosenescence

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Abstract

Gene therapy exhibits the potential to turn back the clock of senescent immune cells. This chapter describes advances in applications of gene therapy to limit immune senescence and potentially to offer temporary and eventually, more permanent approaches to reversal of the senescence process. Work on current gene therapy vectors including adenovirus, adeno-associated virus (AAV), retrovirus, and nonviral gene therapy is described. The advantages and disadvantages to these different therapies, including a short-term or temporary reversal of cell senescence and the importance to avoid the occurrence of cancer, are discussed. Newly developed approaches use CRISPR/Cas to directly target and correct genes that promote cell senescence, and these are often utilized in combination with AAV gene therapy for cell senescent treatment. Cell-based gene therapy includes the use of CD34+ stem cells for potential long-term repopulation of bone marrow that can lead to further differentiation in the thymus and periphery of T cells, B cells, and macrophages. Recently, cell gene therapy is developed to reprogram induced pluripotent stem cells (iPSC) to provide perfectly matched donor cells to replace the aging cells with one’s own “youthful” cells. Applications through generation of T cells, both in the thymus and cytotoxic T cells, in the periphery are described. Factors that promote “inflammation” in mechanisms to limit the damage of inflammation on cell senescence are discussed. Finally, recent advances with gene therapy related to telomerase reverse transcriptase, such as AAV gene therapy, which has been shown to result in lengthening of telomeres, are described.

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Authors and Affiliations

  1. Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, School of Medicine, Birmingham, AL, USA

    Hui-Chen Hsu & John D. Mountz

  2. Department of Clinical Transfusion Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Jian Chen

  3. Birmingham VA Medical Center, Birmingham, AL, USA

    John D. Mountz

Authors
  1. Hui-Chen Hsu
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  2. Jian Chen
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  3. John D. Mountz
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Corresponding author

Correspondence to John D. Mountz .

Editor information

Editors and Affiliations

  1. Division of Geriatrics Research Center on Aging, University of Sherbrooke Dept. of Medicine, Sherbrooke, Québec, Canada

    Tamas Fulop

  2. Dept of Experimental Pathology, University of Bologna, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, Tokyo, Japan

    Katsuiku Hirokawa

  4. Center for Medical Research, University of Tübingen, Tübingen, Germany

    Graham Pawelec

Section Editor information

  1. Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Tamas Fulop

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Hsu, HC., Chen, J., Mountz, J.D. (2018). Gene Therapy and Immunosenescence. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook of Immunosenescence. Springer, Cham. https://doi.org/10.1007/978-3-319-64597-1_76-1

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  • DOI: https://doi.org/10.1007/978-3-319-64597-1_76-1

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