8型AAV重组病毒介导的凝血因子的基因表达
DOI:
CSTR:
作者:
作者单位:

作者简介:

通讯作者:

中图分类号:

基金项目:

国家自然科学基金部分资助项目(30271370).


Study on The Expression of Coagulation Factor Mediated by Recombinant AAV Serotype 8
Author:
Affiliation:

Fund Project:

This work was supported by a grant from The National Natural Science Foundation of China (30271370).

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    8型AAV重组病毒载体是新型的基因转移载体,能高效转染肌肉细胞和肝细胞. AAV转染细胞的效果与注射病毒的途径有很大关系. 与门脉注射和肌肉注射相比,经腹腔注射的rAAV8病毒能经血液循环转运到全身其他组织器官,形成更加广泛和持久的基因转导. 通过腹腔途径把5×1010 gc的8型重组病毒载体注射到小鼠体内,2周后,小鼠血浆中有明显的基因表达,1个月至2个月期间多数小鼠表达量达到高峰,然后表达水平下降,直到4个月后血浆中尚维持明显的表达量. 凝血实验显示,表达的人凝血因子Ⅸ具有生物活性. 免疫组化实验显示,病毒载体已进入体内多组织器官中表达. 说明8型AAV病毒载体经腹腔注射后已经血液循环运送到其他组织,并在肌肉、肝脏、肾脏和心脏等器官明显表达,表达产物具有凝血活性.

    Abstract:

    Recombinant AAV serotype 8 (rAAV8) vector is new and promising for gene delivery,which transduces muscular and hepatic cells highly efficiently. The transduction varies with the administration routes. It was observed that the rAAV8 virus injected intraperitoneally had been delivered to many different tissues through the blood circulation and resulted in extensive and prolonged gene expression. The interest gene (human coagulation factor Ⅸ) has been highly expressed via the rAAV8 vector injected intraperitoneally into mice at the dose of 5×1010 gc/ mouse. Considerable expression was detected in mouse plasma at two weeks after the administration. Expression peak up to 1 000% level compared to the UCRP occurred between 1~2 months after administration, and then the expression declined gradually but obvious expression persisted at 4 months post administration. APTT test proved the clotting activity of the recombinant hFⅨ in mouse plasma. Immunohistochemical assay showed that the human coagulation factor has been expressed significantly in several organs including liver, kidney, heart and muscles (abdominal and hindleg). These suggest that the rAAV8 virus injected intraperitoneally has been delivered via blood circulation and transduced different cells of multi-organs, and the product of the gene mediated by the rAAV8 vector is biologically active.

    参考文献
    相似文献
    引证文献
引用本文

曹佐武,李观贵,梁郁强,何冬梅.8型AAV重组病毒介导的凝血因子的基因表达[J].生物化学与生物物理进展,2007,34(1):80-86

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2006-06-13
  • 最后修改日期:2006-10-31
  • 接受日期:
  • 在线发布日期: 2007-01-15
  • 出版日期: