Zylberberg C, Gaskill K, Pasley S, Matosevic S
Akron Biotech, Boca Raton, FL, USA.
Gene Ther. 2017 Aug;24(8):441-452. doi: 10.1038/gt.2017.41. Epub 2017 May 15.
Recent mechanistic studies have attempted to deepen our understanding of the process by which liposome-mediated delivery of genetic material occurs. Understanding the interactions between lipid nanoparticles and cells is still largely elusive. Liposome-mediated delivery of genetic material faces systemic obstacles alongside entry into the cell, endosomal escape, lysosomal degradation and nuclear uptake. Rational design approaches for targeted delivery have been developed to reduce off-target effects and enhance transfection. These strategies, which have included the modification of lipid nanoparticles with target-specific ligands to enhance intracellular uptake, have shown significant promise at the proof-of-concept stage. Control of physical and chemical specifications of liposome composition, which includes lipid-to-DNA charge, size, presence of ester bonds, chain length and nature of ligand complexation, is integral to the performance of targeted liposomes as genetic delivery agents. Clinical advances are expected to rely on such systems in the therapeutic application of liposome nanoparticle-based gene therapy. Here, we discuss the latest breakthroughs in the development of targeted liposome-based agents for the delivery of genetic material, paying particular attention to new ligand and cationic lipid design as well as recent in vivo advances.
最近的机制研究试图加深我们对脂质体介导的遗传物质递送过程的理解。了解脂质纳米颗粒与细胞之间的相互作用在很大程度上仍然难以捉摸。脂质体介导的遗传物质递送除了进入细胞、内体逃逸、溶酶体降解和核摄取外，还面临全身障碍。已开发出靶向递送的合理设计方法，以减少脱靶效应并增强转染。这些策略，包括用靶向特异性配体修饰脂质纳米颗粒以增强细胞内摄取，在概念验证阶段已显示出巨大的前景。脂质体组成的物理和化学特性的控制，包括脂质与DNA的电荷、大小、酯键的存在、链长和配体络合的性质，对于靶向脂质体作为基因递送剂的性能至关重要。临床进展有望依赖于此类系统在基于脂质体纳米颗粒的基因治疗的治疗应用中。在此，我们讨论了用于遗传物质递送的靶向脂质体基药物开发的最新突破，特别关注新的配体和阳离子脂质设计以及最近的体内进展。
