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

8 Citations (Scopus)

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

Fingerprint

T-cells
Interleukin-17
Small Interfering RNA
T-Lymphocytes
Th17 Cells
RNA Interference
Transcription
Ribonucleases
Gene expression
Cell Differentiation
Complementary DNA
RNA
Gene Expression

Keywords

  • Aptamer-shRNA
  • RORγt
  • Th17

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Song, P., Chou, Y. K., Zhang, X., Meza-Romero, R., Yomogida, K., Benedek, G., & Chu, C-Q. (2014). CD4 aptamer-RORγt shRNA chimera inhibits IL-17 synthesis by human CD4+ T cells. Biochemical and Biophysical Research Communications, 452(4), 1040-1045. https://doi.org/10.1016/j.bbrc.2014.09.037

CD4 aptamer-RORγt shRNA chimera inhibits IL-17 synthesis by human CD4+ T cells. / Song, Pingfang; Chou, Yuan K.; Zhang, Xiaowei; Meza-Romero, Roberto; Yomogida, Kentaro; Benedek, Gil; Chu, Cong-Qiu.

In: Biochemical and Biophysical Research Communications, Vol. 452, No. 4, 03.10.2014, p. 1040-1045.

Research output: Contribution to journalArticle

Song, P, Chou, YK, Zhang, X, Meza-Romero, R, Yomogida, K, Benedek, G & Chu, C-Q 2014, 'CD4 aptamer-RORγt shRNA chimera inhibits IL-17 synthesis by human CD4+ T cells', Biochemical and Biophysical Research Communications, vol. 452, no. 4, pp. 1040-1045. https://doi.org/10.1016/j.bbrc.2014.09.037
Song, Pingfang ; Chou, Yuan K. ; Zhang, Xiaowei ; Meza-Romero, Roberto ; Yomogida, Kentaro ; Benedek, Gil ; Chu, Cong-Qiu. / CD4 aptamer-RORγt shRNA chimera inhibits IL-17 synthesis by human CD4+ T cells. In: Biochemical and Biophysical Research Communications. 2014 ; Vol. 452, No. 4. pp. 1040-1045.
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