McCullough Kenneth C, Bassi Isabelle, Démoulins Thomas, Thomann-Harwood Lisa J, Ruggli Nicolas
Institute of Virology & Immunoprophylaxis, CH-3147 Mittelhäusern, Switzerland.
Ther Deliv. 2012 Sep;3(9):1077-99. doi: 10.4155/tde.12.90.
Dendritic cells (DCs) are essential to many aspects of immune defense development and regulation. They provide important targets for prophylactic and therapeutic delivery. While protein delivery has had considerable success, RNA delivery is still expanding. Delivering RNA molecules for RNAi has shown particular success and there are reports on successful delivery of mRNA. Central, therein, is the application of cationic entities. Following endocytosis of the delivery vehicle for the RNA, cationic entities should promote vesicular membrane perturbation, facilitating cytosolic release. The present review explains the diversity of DC function in immune response development and control. Promotion of delivered RNA cytosolic release is discussed, relating to immunoprophylactic and therapeutic potential, and DC endocytic machinery is reviewed, showing how DC endocytic pathways influence the handling of internalized material. The potential advantages for application of replicating RNA are presented and discussed, in consideration of their value and development in the near future.
树突状细胞(DCs)在免疫防御的发展和调节的许多方面都至关重要。它们为预防性和治疗性递送提供了重要靶点。虽然蛋白质递送已取得相当大的成功,但RNA递送仍在不断发展。用于RNA干扰的RNA分子递送已显示出特别的成功,并且有关于成功递送mRNA的报道。其中的核心是阳离子实体的应用。在RNA递送载体被内吞后,阳离子实体应促进囊泡膜扰动,便于胞质释放。本综述解释了DC在免疫反应发展和控制中的功能多样性。讨论了促进递送的RNA胞质释放与免疫预防和治疗潜力的关系,并综述了DC内吞机制,展示了DC内吞途径如何影响内化物质的处理。考虑到复制RNA在不久的将来的价值和发展,介绍并讨论了其应用的潜在优势。