CD4 aptamer-RORγt shRNA chimera inhibits IL-17 synthesis by human CD4+ T cells

Pingfang Song, Yuan K. Chou, Xiaowei Zhang, Roberto Meza-Romero, Kentaro Yomogida, Gil Benedek, Cong Qiu Chu

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1040-1045
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume452
Issue number4
DOIs
StatePublished - Oct 3 2014
Externally publishedYes

Keywords

  • Aptamer-shRNA
  • RORγt
  • Th17

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