The Interaction Mechanism of Intramuscular Gene Delivery Materials with Cell Membranes.

The Interaction Mechanism of Intramuscular Gene Delivery Materials with Cell Membranes.
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DOI:
10.3390/jfb14040219
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发表时间:
2023-04-14
影响因子:
4.8
通讯作者:
--
中科院分区:
工程技术3区
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--
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已经证实骨骼肌细胞具有接受外源质粒DNA(pDNA)并表达功能蛋白的能力。这为安全、方便、经济的基因治疗提供了一种有希望的适用策略。然而,肌内pDNA递送效率对于大多数治疗目的而言不够高。一些非病毒生物材料,特别是几种两亲性三嵌段共聚物,已被证明可以显着提高肌内基因递送效率,但详细的过程和机制仍然没有得到很好的理解。本研究采用分子动力学模拟方法,在原子和分子水平上研究了材料分子、细胞膜和DNA分子的结构和能量变化。结果揭示了材料分子与细胞膜的相互作用过程和机理,更重要的是,模拟结果与以往的实验结果几乎完全吻合。本研究有助于我们设计和优化更好的肌内基因递送材料,以用于临床应用。
It has been confirmed that skeletal muscle cells have the capability to receive foreign plasmid DNA (pDNA) and express functional proteins. This provides a promisingly applicable strategy for safe, convenient, and economical gene therapy. However, intramuscular pDNA delivery efficiency was not high enough for most therapeutic purposes. Some non-viral biomaterials, especially several amphiphilic triblock copolymers, have been shown to significantly improve intramuscular gene delivery efficiency, but the detailed process and mechanism are still not well understood. In this study, the molecular dynamics simulation method was applied to investigate the structure and energy changes of the material molecules, the cell membrane, and the DNA molecules at the atomic and molecular levels. From the results, the interaction process and mechanism of the material molecules with the cell membrane were revealed, and more importantly, the simulation results almost completely matched the previous experimental results. This study may help us design and optimize better intramuscular gene delivery materials for clinical applications.
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