Xu Peisheng, Quick Griffin K, Yeo Yoon
Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
Biomaterials. 2009 Oct;30(29):5834-43. doi: 10.1016/j.biomaterials.2009.07.012. Epub 2009 Jul 25.
For a non-viral gene delivery system to be clinically effective, it should be non-toxic, compatible with biological components, and highly efficient in gene transfection. With this goal in mind, we investigated the gene delivery efficiency of a ternary complex consisting of DNA, an intracellularly degradable polycation, and sodium hyaluronate (DPH complex). Here, we report that the DPH ternary complex achieved significantly higher transfection efficiency than other polymer systems, especially in the presence of serum. The high transfection efficiency and serum tolerance of DPH are attributed to a unique interplay between CLPEI and HA, which leads to (i) the improved stability of DNA in the extracellular environment and at the early stage of intracellular trafficking and (ii) timely dissociation of the DNA-polymer complex. This study reinforces findings of earlier studies that emphasized each step as a bottleneck for efficient gene delivery; yet, it is the first to show that it is possible to overcome these obstacles simultaneously by taking advantage of two distinctive approaches.
要使非病毒基因递送系统在临床上有效，它应无毒、与生物成分兼容且在基因转染方面高效。出于这一目标，我们研究了由DNA、细胞内可降解聚阳离子和透明质酸钠组成的三元复合物（DPH复合物）的基因递送效率。在此，我们报告DPH三元复合物实现了比其他聚合物系统显著更高的转染效率，尤其是在血清存在的情况下。DPH的高转染效率和血清耐受性归因于CLPEI和HA之间独特的相互作用，这导致（i）DNA在细胞外环境和细胞内运输早期的稳定性提高，以及（ii）DNA-聚合物复合物的及时解离。这项研究强化了早期研究的结果，这些研究强调每个步骤都是高效基因递送的瓶颈；然而，它首次表明通过利用两种不同的方法有可能同时克服这些障碍。
