• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文会议> >Integrating molecular thermodynamics and systems biology to improve the cellular effectiveness of antisense oligonucleotides
【24h】

Integrating molecular thermodynamics and systems biology to improve the cellular effectiveness of antisense oligonucleotides

机译：整合分子热力学和系统生物学，以提高反义寡核苷酸的细胞效力

获取原文
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Antisense oligonucleotides (AS ONs) are a powerful means to inhibit the expression of specific genes, but their effectiveness is limited by factors including cellular delivery, biochemical attack, and poor binding to target. We have developed a systems model of the processes required for an antisense oligonucleotide to be successfully delivered and to exert activity in a cell. The model demonstrates a sensitive dependence of the extent of gene expression inhibition on the binding rate for the ON-mRNA interaction. We have focused on the binding event and developed a molecular thermodynamic model based on ON and mRNA folding that predicts accurately the affinity of ON-mRNA binding, and we have observed experimentally that affinity correlates directly with binding rate for these species. Most importantly, we have found that the model successfully selects those ONs that are most successful in cell culture. Taken together, these tools may help accelerate the development of this promising technology.
机译：反义寡核苷酸（AS ONs）是抑制特定基因表达的有力手段，但其有效性受到细胞递送，生化攻击和与靶标结合力差等因素的限制。我们已经开发了反义寡核苷酸成功传递并在细胞中发挥活性所需的过程的系统模型。该模型证明了基因表达抑制程度对ON-mRNA相互作用结合率的敏感依赖性。我们专注于结合事件，并开发了基于ON和mRNA折叠的分子热力学模型，该模型可准确预测ON-mRNA结合的亲和力，并且我们通过实验观察到，亲和力与这些物种的结合率直接相关。最重要的是，我们发现该模型成功选择了在细胞培养中最成功的ON。综上所述，这些工具可能有助于加速这项有前途的技术的发展。

著录项

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