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    Self-Assembly of a Virus-Mimicking Nanostructure System for Efficient Tumor-Targeted Gene Delivery

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    XuLiang_HGT_13(3)469.pdf (1.704Mb)
    Issue Date
    2002-02-10
    Author
    Xu, Liang
    Frederik, Peter
    Pirollo, Kathleen F.
    Tang, Wen-Hua
    Rait, Antonina
    Xiang, Lai-Man
    Huang, Weiqun
    Cruz, Idalia
    Yin, Yuzhi
    Chang, Esther H.
    Publisher
    Mary Ann Liebert
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Metadata
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    Abstract
    Molecular therapy, including gene therapy, is a promising strategy for the treatment of human disease. However, delivery of molecular therapeutics efficiently and specifically to the target tissue remains a significant challenge. A human transferrin (Tf)-targeted cationic liposome-DNA complex, Tf-lipoplex, has shown high gene transfer efficiency and efficacy with human head and neck cancer in vitro and in vivo (Xu, L., Pirollo, K.F., Tang, W.H., Rait, A., and Chang, E.H. Hum. Gene Ther. 1999;10:2941-2952). Here we explore the structure, size, formation process, and structure-function relationships of Tf-lipoplex. We have observed Tf-lipoplex to have a highly compact structure, with a relatively uniform size of 50-90 nm. This nanostructure is novel in that it resembles a virus particle with a dense core enveloped by a membrane coated with Tf molecules spiking the surface. More importantly, compared with unliganded lipoplex, Tf-lipoplex shows enhanced stability, improved in vivo gene transfer efficiency, and long-term efficacy for systemic p53 gene therapy of human prostate cancer when used in combination with conventional radiotherapy. On the basis of our observations, we propose a multistep self-assembly process and Tf-facilitated DNA cocondensation model that may provide an explanation for the resultant small size and effectiveness of our nanostructural Tf-lipoplex system.
    Description
    This is the published version, also available here: http://dx.doi.org/10.1089/10430340252792594.
    URI
    http://hdl.handle.net/1808/17359
    DOI
    https://doi.org/10.1089/10430340252792594
    Collections
    • Molecular Biosciences Scholarly Works [590]
    Citation
    Liang Xu, Peter Frederik, Kathleen F. Pirollo, Wen-Hua Tang, Antonina Rait, Lai-Man Xiang, Weiqun Huang, Idalia Cruz, Yuzhi Yin, and Esther H. Chang. Human Gene Therapy. February 2002, 13(3): 469-481. http://dx.doi.org/10.1089/10430340252792594.

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    KU Libraries
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    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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