Sustained GM-CSF and PEI condensed pDNA presentation increases the level and duration of gene expression in dendritic cells
Sustained GM-CSF and PEI condensed pDNA presentation increases the level and duration of gene expression in dendritic cells
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DOI：
10.1016/j.jconrel.2008.07.005
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发表时间：
2008-12-18
影响因子：
10.8
通讯作者：
Mooney, David J.
中科院分区：
文献类型：
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作者：
Ali, Omar A.;Mooney, David J.
目前用于离体培养树突状细胞（DC）用于免疫治疗的技术受到低效方案的困扰，并且DC修饰通常是短暂的并且在移植时丢失。本研究探讨了GM-CSF和PEI浓缩的pDNA（PEI-DNA）的持续呈递对基因转移和长期基因表达的作用。在DC转染期间适当的GM-CSF信号传导促进PEI-DNA摄取，尽管高细胞因子浓度诱导细胞间DNA降解，表明需要受控呈递。聚（丙交酯-共-乙交酯）支架，连续刺激树突状细胞与GM-CSF和PEI-DNA导致20倍的基因表达增加，高水平的表达持续了10天的时间，在体外。这些结果鼓励利用生物材料和GM-CSF开发用于遗传修饰DC的新型递送载体或原位遗传编程宿主DC用于疫苗接种和自身免疫治疗。(C)2008 Elsevier B. V.保留所有权利。
Current techniques to educate dendritic cells (DCs) ex vivo for immunotherapy are plagued by inefficient protocols and DC modifications are often transient and lost upon transplantation. This study investigated the role of sustained presentation of GM-CSF and PEI condensed pDNA (PEI-DNA) on gene transfer and long-term gene expression. Appropriate GM-CSF signaling during DC transfection promoted PEI-DNA uptake, although high cytokine concentrations induced intercellular DNA degradation, indicating the need for controlled presentation. Poly(lactide-co-glycolide) scaffolds that continuously stimulated DCs with both GM-CSF and PEI-DNA led to a 20-fold increase in gene expression, and high levels of expression persisted for a period of 10 days, in vitro. These results encourage the exploitation of biomaterials and GM-CSF to develop novel delivery vectors for genetically modified DCs or to genetically program host DCs in situ for vaccination and the treatment of autoimmunity. (C) 2008 Elsevier B.V. All rights reserved.