• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Advanced Functional Materials >A Gene Therapy Technology-Based Biomaterial for the Trigger-Inducible Release of Biopharmaceuticals in Mice
【24h】

A Gene Therapy Technology-Based Biomaterial for the Trigger-Inducible Release of Biopharmaceuticals in Mice

机译：基于基因治疗技术的生物材料，用于触发诱导型生物药物在小鼠体内的释放

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Gene therapy scientists have developed expression systems for therapeutic transgenes within patients, which must be seamlessly integrated into the patient's physiology by developing sophisticated control mechanisms to titrate expression levels of the transgenes into the therapeutic window. However, despite these efforts, gene-based medicine still faces security concerns related to the administration of the therapeutic transgene vector. Here, molecular tools developed for therapeutic transgene expression can readily be transferred to materials science to design a humanized drug depot that can be implanted into mice and enables the trigger-inducible release of a therapeutic protein in response to a small-molecule inducer. The drug depot is constructed by embedding the vascular endothelial growth factor (VEGF_(121)) as model therapeutic protein into a hydrogel consisting of linear polyacrylamide crosslinked with a homodimeric variant of the human FK-binding protein 12 (F_M), originally developed for gene therapeutic applications, as well as with dimethylsuberimidate. Administrating increasing concentrations of the inducer molecule FK506 triggers the dissociation of F_M thereby loosening the hydrogel structure and releasing the VEGF_(121) payload in a dose-adjustable manner. Subcutaneous implantation of the drug depot into mice and subsequent administration of the inducer by injection or by oral intake triggers the release of VEGF_(121) as monitored in the mouse serum. This study is the first demonstration of a stimuli-responsive hydrogel that can be used in mammals to release a therapeutic protein on demand by the application of a small-molecule stimulus. This trigger-inducible release is a starting point for the further development of externally controlled drug depots for patient-compliant administration of biopharmaceuticals.
机译：基因治疗科学家已经开发出用于患者体内治疗性转基因的表达系统，必须通过开发复杂的控制机制以将转基因的表达水平滴定到治疗范围内，将其无缝整合到患者的生理中。然而，尽管做出了这些努力，基于基因的药物仍然面临与治疗性转基因载体的给药有关的安全性问题。在这里，为治疗性转基因表达而开发的分子工具可以很容易地转移到材料科学领域，以设计人源化的药物仓库，该仓库可以植入小鼠体内，并且能够响应小分子诱导物而触发性诱导释放治疗性蛋白质。通过将作为模型治疗蛋白的血管内皮生长因子（VEGF_（121））嵌入到由线性聚丙烯酰胺与人类FK结合蛋白12（F_M）的同型二聚体变体交联而成的水凝胶中来构建药物仓库治疗应用，以及与亚甲基次亚磺酸酯。给予增加浓度的诱导剂分子FK506会触发F_M的解离，从而使水凝胶结构松散并以剂量可调的方式释放VEGF_（121）有效负载。如在小鼠血清中监测的，将药物库皮下植入小鼠体内并随后通过注射或口服摄入诱导剂来触发VEGF_（121）的释放。这项研究是对刺激反应性水凝胶的首次展示，该水凝胶可通过应用小分子刺激物，用于哺乳动物按需释放治疗性蛋白质。这种触发诱导型释放是进一步开发用于患者依从性给药生物药物的外部控制药物仓库的起点。

著录项

  • 来源
    《Advanced Functional Materials》 |2010年第15期|P.2534-2538|共5页
  • 作者

    Michael M. Kaempf; rnErik H. Christen; rnMartin Ehrbar; rnMarie Daoud-El Baba; rnGhislaine Charpin-El Hamri; rnMartin Fussenegger; rnWilfried Weber;

  • 作者单位

    Department of Biosystems Science and Engineering, ETH Zurich Mattenstrasse 26, 4058 Basel (Switzerland);

    rnDepartment of Biosystems Science and Engineering, ETH Zurich Mattenstrasse 26, 4058 Basel (Switzerland);

    rnDepartment of Obstetrics, University Hospital Zurich Frauenklinikstrasse 10, 8091 Zurich (Switzerland);

    rnUniversite de Lyon 69622 Lyon (France);

    rnUniversite de Lyon 69622 Lyon (France);

    rnDepartment of Biosystems Science and Engineering, ETH Zurich Mattenstrasse 26, 4058 Basel (Switzerland);

    rnCentre for Biological Signalling Studies/Faculty of Biology, Albert-Ludwigs-Universitaet Freiburg Engesserstrasse 4b, 79108 Freiburg (Germany);

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号