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New generation of plasmid backbones devoid of antibiotic resistance marker for gene therapy trials

cyzhgt 添加于 2011-11-22 15:19 | 1499 次阅读 | 0 个评论
  •  作 者

    Vandermeulen G, Marie C, Scherman D, Preat V
  •  摘 要

    Since it has been established that the injection of plasmid DNA can lead to an efficient expression of a specific protein in vivo, nonviral gene therapy approaches have been considerably improved, allowing clinical trials. However, the use of antibiotic resistance genes as selection markers for plasmid production raises safety concerns which are often pointed out by the regulatory authorities. Indeed, a horizontal gene transfer to patient's bacteria cannot be excluded, and residual antibiotic in the final product could provoke allergic reactions in sensitive individuals. A new generation of plasmid backbones devoid of antibiotic resistance marker has emerged to increase the safety profile of nonviral gene therapy trials. This article reviews the existing strategies for plasmid maintenance and, in particular, those that do not require the use of antibiotic resistance genes. They are based either on the complementation of auxotrophic strain, toxin-antitoxin systems, operator-repressor titration, RNA markers, or on the overexpression of a growth essential gene. Minicircles that allow removing of the antibiotic resistance gene from the initial vector will also be discussed. Furthermore, reported use of antibiotic-free plasmids in preclinical or clinical studies will be listed to provide a comprehensive view of these innovative technologies.
  •  详细资料

    • 文献种类:期刊
    • 期刊名称: Molecular Therapy : the Journal of the American Society of Gene Therapy
    • 期刊缩写: Mol Ther
    • 期卷页: 2011  19 11 1942-1949
    • 地址: Universite catholique de Louvain, Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, Brussels, Belgium
    • ISBN: 1525-0016
    • 备注:PMID:21878901
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