CD154
树突状细胞
CD40
抗原提呈细胞
细胞生物学
材料科学
免疫系统
癌症研究
移植
T细胞
体外
化学
医学
生物
免疫学
细胞毒性T细胞
生物化学
外科
作者
Yue Zhang,Song Shen,Gui Zhao,Cong‐Fei Xu,Houbing Zhang,Ying‐Li Luo,Zhi‐Ting Cao,Jia Shi,Zhibin Zhao,Zhe‐Xiong Lian,Jun Wang
出处
期刊:Biomaterials
[Elsevier BV]
日期:2019-06-24
卷期号:217: 119302-119302
被引量:78
标识
DOI:10.1016/j.biomaterials.2019.119302
摘要
Organ transplantation is the only effective method to treat end-stage organ failure. However, it is continuously plagued by immune rejection, which is mostly caused by T cell-mediated reactions. Dendritic cells (DCs) are professional antigen-presenting cells, and blocking the costimulatory signaling molecule CD40 in DCs inhibits T cell activation and induces transplant tolerance. In this study, to relieve graft rejection, Cas9 mRNA (mCas9) and a guide RNA targeting the costimulatory molecule CD40 (gCD40) were prepared and encapsulated into poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-b-PLGA)-based cationic lipid-assisted nanoparticles (CLAN), denoted CLANmCas9/gCD40. CLAN effectively delivered mCas9/gCD40 into DCs and disrupted CD40 in DCs at the genomic level both in vitro and in vivo. After intravenous injection into an acute mouse skin transplant model, CLANmCas9/gCD40-mediated CD40 disruption significantly inhibited T cell activation, which reduced graft damage and prolonged graft survival. This work provides a promising strategy for reprogramming DCs with nanoparticles carrying the CRISPR/Cas9 system to abate transplant rejection.
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