International Joint Center for Biomedical Innovation, School of Life Sciences, Henan University , Kaifeng, Henan 475004, P.R. China.
Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02115, United States.
Biomacromolecules. 2017 Aug 14;18(8):2231-2246. doi: 10.1021/acs.biomac.7b00803. Epub 2017 Jul 14.
After more than 20 years of intensive investigations, gene therapy has become one of the most promising strategies for treating genetic diseases. However, the lack of ideal delivery systems has limited the clinical realization of gene therapy's tremendous potential, especially for DNA-based gene therapy. Over the past decade, considerable advances have been made in the application of polymer-based DNA delivery systems for gene therapy, especially through multifunctional systems. The core concept behind multifunctional polymeric DNA delivery systems is to endow one single DNA carrier, via materials engineering and surface modification, with several active functions, e.g., good cargo DNA protection, excellent colloidal stability, high cellular uptake efficiency, efficient endo/lysosome escape, effective import into the nucleus, and DNA unpacking. Such specially developed vectors would be capable of overcoming multiple barriers to the successful delivery of DNA. In this review, we first provide a comprehensive overview of the interactions between the protein corona and DNA vectors, the mechanisms and challenges of nonviral DNA vectors, and important concepts in the design of DNA carriers identified via past reports on DNA delivery systems. Finally, we highlight and discuss recent advances in multifunctional polymeric DNA delivery systems based on "off-the-shelf" polycations including polyethylenimine (PEI), poly-l-lysine (PLL), and chitosan and offer perspectives on future developments.
经过二十多年的深入研究，基因治疗已成为治疗遗传疾病最有前途的策略之一。然而，缺乏理想的输送系统限制了基因治疗巨大潜力的临床实现，特别是对于基于 DNA 的基因治疗。在过去的十年中，聚合物基 DNA 输送系统在基因治疗中的应用取得了相当大的进展，特别是通过多功能系统。多功能聚合物 DNA 输送系统的核心概念是通过材料工程和表面修饰，赋予单一的 DNA 载体几种活性功能，例如，良好的货物 DNA 保护、优异的胶体稳定性、高细胞摄取效率、有效的内体/溶酶体逃逸、有效导入细胞核和 DNA 解包。这种专门开发的载体将能够克服 DNA 成功传递的多个障碍。在这篇综述中，我们首先全面概述了蛋白质冠与 DNA 载体之间的相互作用、非病毒 DNA 载体的机制和挑战，以及通过过去关于 DNA 传递系统的报告确定的 DNA 载体设计的重要概念。最后，我们强调并讨论了基于“现成”聚阳离子（包括聚乙烯亚胺 (PEI)、聚赖氨酸 (PLL) 和壳聚糖）的多功能聚合物 DNA 输送系统的最新进展，并对未来的发展提出了展望。
