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Components Simulation of Viral Envelope via Amino Acid Modified Chitosans for Efficient Nucleic Acid Delivery: In Vitro and In Vivo Study

Authors

  • Jing Chang,

    1. National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, P. R. China
    2. College of Marine Life Science, Ocean University of China, Qingdao 266003, P. R. China
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  • Xianghui Xu,

    1. National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, P. R. China
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  • Haiping Li,

    1. National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, P. R. China
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  • Yeting Jian,

    1. National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, P. R. China
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  • Gang Wang,

    1. National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, P. R. China
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  • Bin He,

    Corresponding author
    1. National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, P. R. China
    • National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, P. R. China.
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  • Zhongwei Gu

    Corresponding author
    1. National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, P. R. China
    • National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, P. R. China.
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Abstract

Novel nonviral gene vectors of alkaline amino acids such as arginine- (Arg), histidine- (His), and lysine- (Lys) modified chitosans (AAA-CSs) are developed to simulate the components of viral envelopes to enhance transfection efficiency. The structures of the modified chitosans are characterized using 1H NMR spectroscopy. Acid-base titration results indicate that the modified chitosans exhibit strong buffering capacity. The morphology of the AAA-CSs/pDNA complexes is observed by use of transmission electron microscopy and atomic force microscopy. The complexes are spherical nanoparticles with a mean size around 100 nm. Zeta potential tests reveal that the complexes are positively charged and their zeta potentials vary from +0.1 to +19.5 mV. The MTT assay and agarose gel electrophoresis demonstrate that the AAA-CSs are non-cytotoxic and have excellent DNA condensation and protection abilities. Cellular uptake investigation of the AAA-CSs/pDNA complexes demonstrates that Arg-CS and His-CS have better cellular internalization property than the unmodified chitosan. The in vitro gene transfection is evaluated in HEK293 and NIH3T3 cell lines and in vivo transfection is carried out in tibialis anterior muscles. The results reveal that the arginine-modified chitosan could significantly enhance gene-transfection efficiency both in vitro and in vivo.

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