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Highly branched poly(β-amino ester) delivery of minicircle DNA for transfection of neurodegenerative disease related cells

Author

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  • Shuai Liu

    (University College Dublin
    Nankai University)

  • Yongsheng Gao

    (University College Dublin)

  • Dezhong Zhou

    (University College Dublin
    Xiʹan Jiaotong University)

  • Ming Zeng

    (University College Dublin)

  • Fatma Alshehri

    (University College Dublin)

  • Ben Newland

    (Cardiff University)

  • Jing Lyu

    (University College Dublin)

  • Jonathan O’Keeffe-Ahern

    (University College Dublin)

  • Udo Greiser

    (University College Dublin)

  • Tianying Guo

    (Nankai University)

  • Fengzhi Zhang

    (Zhejiang University of Technology)

  • Wenxin Wang

    (University College Dublin
    Zhejiang University)

Abstract

Current therapies for most neurodegenerative disorders are only symptomatic in nature and do not change the course of the disease. Gene therapy plays an important role in disease modifying therapeutic strategies. Herein, we have designed and optimized a series of highly branched poly(β-amino ester)s (HPAEs) containing biodegradable disulfide units in the HPAE backbone (HPAESS) and guanidine moieties (HPAESG) at the extremities. The optimized polymers are used to deliver minicircle DNA to multipotent adipose derived stem cells (ADSCs) and astrocytes, and high transfection efficiency is achieved (77% in human ADSCs and 52% in primary astrocytes) whilst preserving over 90% cell viability. Furthermore, the top-performing candidate mediates high levels of nerve growth factor (NGF) secretion from astrocytes, causing neurite outgrowth from a model neuron cell line. This synergistic gene delivery system provides a viable method for highly efficient non-viral transfection of ADSCs and astrocytes.

Suggested Citation

  • Shuai Liu & Yongsheng Gao & Dezhong Zhou & Ming Zeng & Fatma Alshehri & Ben Newland & Jing Lyu & Jonathan O’Keeffe-Ahern & Udo Greiser & Tianying Guo & Fengzhi Zhang & Wenxin Wang, 2019. "Highly branched poly(β-amino ester) delivery of minicircle DNA for transfection of neurodegenerative disease related cells," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11190-0
    DOI: 10.1038/s41467-019-11190-0
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