"Programmed packaging" for gene delivery
"Programmed packaging" for gene delivery
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DOI：
10.1016/j.jconrel.2014.04.023
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发表时间：
2014-11-10
影响因子：
10.8
通讯作者：
Harashima, H.
中科院分区：
文献类型：
--
作者：
Hyodo, M.;Sakurai, Y.;Harashima, H.
我们报道了一种基于我们的包装概念的多功能包膜型纳米器件(MEND)的开发，该器件不仅可以控制细胞内的运输，还可以控制被包裹的化合物的生物分布，如核酸/蛋白质/多肽。我们实现这一目标的策略是基于细胞生物学的分子机制，如内吞作用、囊泡运输等。在这篇综述中，我们总结了程序化包装的概念，并讨论了我们最近使用Mend的一些成功例子。通过指数富集法系统进化配体(SELEX)作为一种新的方法被应用于向细胞或线粒体鉴定新的配体。利用在体内条件下新设计和优化的pH敏感脂质(YSK05)，实现了siRNA对肿瘤和肿瘤血管的传递。使用Kala配体也开发了将PDNA高效地运送到树突状细胞等免疫细胞的技术，这可能是DNA疫苗的一项突破性技术。最后，还介绍了一种具有pH可激活和SS可切割性质的类脂材料--可裂解和pH激活的类脂表面活性剂(SsPalm)，以验证我们的概念。(C)2014爱思唯尔B.V.保留所有权利。
We report on the development of a multifunctional envelope-type nano device (MEND) based on our packaging concept "Programmed packaging" to control not only intracellular trafficking but also the biodistribution of encapsulated compounds such as nucleic acids/proteins/peptides. Our strategy for achieving this is based on molecular mechanisms of cell biology such as endocytosis, vesicular trafficking, etc. In this review, we summarize the concept of programmed packaging and discuss some of our recent successful examples of using MENDs. Systematic evolution of ligands by exponential enrichment (SELEX) was applied as a new methodology for identifying a new ligand toward cell or mitochondria. The delivery of siRNA to tumors and the tumor vasculature was achieved using pH sensitive lipid (YSK05), which was newly designed and optimized under in vivo conditions. The efficient delivery of pDNA to immune cells such as dendritic cells has also been developed using the KALA ligand, which can be a breakthrough technology for DNA vaccine. Finally, ss-cleavable and pH-activated lipid-like surfactant (ssPalm) which is a lipid like material with pH-activatable and SS-cleavable properties is also introduced as a proof of our concept. (C) 2014 Elsevier B.V. All rights reserved.