Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences , University of Basel , Klingelbergstrasse 50 , 4056 Basel , Switzerland.
Department of Biochemistry and Molecular Biology , University of British Columbia , 2350 Health Sciences Mall , Vancouver , British Columbia V6T 1Z3 , Canada.
ACS Nano. 2019 Apr 23;13(4):3754-3782. doi: 10.1021/acsnano.8b07858. Epub 2019 Apr 2.
Gene therapy is a promising strategy for the treatment of monogenic disorders. Non-viral gene delivery systems including lipid-based DNA therapeutics offer the opportunity to deliver an encoding gene sequence specifically to the target tissue and thus enable the expression of therapeutic proteins in diseased cells. Currently, available gene delivery approaches based on DNA are inefficient and require improvements to achieve clinical utility. In this Review, we discuss state-of-the-art lipid-based DNA delivery systems that have been investigated in a preclinical setting. We emphasize factors influencing the delivery and subsequent gene expression in vitro, ex vivo, and in vivo. In addition, we cover aspects of nanoparticle engineering and optimization for DNA therapeutics. Finally, we highlight achievements of lipid-based DNA therapies in clinical trials.
基因治疗是治疗单基因疾病的一种很有前途的策略。非病毒基因传递系统，包括基于脂质的 DNA 疗法，提供了将编码基因序列特异性递送至靶组织的机会，从而使治疗蛋白在患病细胞中表达。目前，基于 DNA 的可用基因传递方法效率低下，需要改进以实现临床应用。在这篇综述中，我们讨论了已在临床前研究中进行研究的最先进的基于脂质的 DNA 传递系统。我们强调了影响体外、离体和体内递送和随后基因表达的因素。此外，我们还涵盖了纳米颗粒工程和 DNA 治疗优化的各个方面。最后，我们强调了基于脂质的 DNA 疗法在临床试验中的成就。
