CD4 aptamer-RORγt shRNA chimera inhibits IL-17 synthesis by human CD4(+) T cells.
CD4 aptamer-RORγt shRNA chimera inhibits IL-17 synthesis by human CD4(+) T cells.
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DOI：
10.1016/j.bbrc.2014.09.037
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发表时间：
2014-10-03
影响因子：
3.1
通讯作者：
Chu, Cong-Qiu
中科院分区：
文献类型：
--
作者：
Song, Pingfang;Chou, Yuan K.;Zhang, Xiaowei;Meza-Romero, Roberto;Yomogida, Kentaro;Benedek, Gil;Chu, Cong-Qiu
RNAi向T细胞的细胞类型特异性递送仍然是一个挑战。在这里，我们描述了一种适体介导的shRNA递送到靶向RORγt的CD 4 + T细胞以抑制Th 17细胞。构建CD 4适配子和RORγt shRNA的cDNA，体外转录获得嵌合CD 4适配子-ROR γt shRNA（CD 4-AshR-RORγt）。2 '-F-dCTP和2'-F-dUTP掺入CD 4-AshR-RORγt中以获得RNA酶抗性。CD 4-AshR-RORγt被CD 4 + Karpas 299细胞和原代人CD 4 + T细胞特异性摄取。CD 4-AshR-RORγt嵌合体的RORγt shRNA部分被Dicer切割并释放。CD 4-AshR-RORγt抑制Karpas 299细胞和CD 4 + T细胞中RORγt基因的表达，从而抑制Th 17细胞的分化和IL-17的产生。这些结果表明，适体促进的shRNA细胞特异性递送代表了有效RNAi递送的新方法，并且有可能被开发用于靶向特定T细胞亚型的治疗剂。
Cell type specific delivery of RNAi to T cells has remained to be a challenge. Here we describe an aptamer mediated delivery of shRNA to CD4+ T cells targeting RORγt to suppress Th17 cells. A cDNA encoding CD4 aptamer and RORγt shRNA was constructed and the chimeric CD4 aptamer-RORγt shRNA (CD4-AshR-RORγt) was generated using in vitro T7 RNA transcription. 2′-F-dCTP and 2′-F-dUTP were incorporated into CD4-AshR-RORγt for RNase resistance. CD4-AshR-RORγt was specifically uptaken by CD4+ Karpas 299 cells and primary human CD4+ T cells. The RORγt shRNA moiety of CD4-AshR-RORγt chimera was cleaved and released by Dicer. Furthermore, CD4-AshR-RORγt suppressed RORγt gene expression in Karpas 299 cells and CD4+ T cells and consequently inhibited Th17 cell differentiation and IL-17 production. These results demonstrate that aptamer-facilitated cell specific delivery of shRNA represents a novel approach for efficient RNAi delivery and is potentially to be developed for therapeutics targeting specific T cells subtypes.
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DOI：
10.1038/labinvest.2009.113
发表时间：
2009-12
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
通讯作者：
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影响因子：
82.9
作者：
Rangachari, Manu;Zhu, Chen;Sakuishi, Kaori;Xiao, Sheng;Karman, Jozsef;Chen, Andrew;Angin, Mathieu;Wakeham, Andrew;Greenfield, Edward A.;Sobel, Raymond A.;Okada, Hitoshi;McKinnon, Peter J.;Mak, Tak W.;Addo, Marylyn M.;Anderson, Ana C.;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.
影响因子：
15.9
作者：
Ni, Xiaohua;Zhang, Yonggang;Lupold, Shawn E.
通讯作者：
Lupold, Shawn E.
影响因子：
3.8
作者：
Yomogida, Kentaro;Chou, Yuan;Chu, Cong-Qiu
通讯作者：
Chu, Cong-Qiu
影响因子：
--
作者：
van Hamburg, J. P.;Asmawidjaja, P. S.;Lubberts, E.
通讯作者：
Lubberts, E.