Stable expression of shRNAs in human CD34+ progenitor cells can avoid induction of interferon responses to siRNAs in vitro

Marjorie A. Robbins, Mingjie Li, Irene Leung, Haitang Li, Doris V. Boyer, Yong Song, Mark A. Behlke, John J. Rossi

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

RNA interference occurs when cytoplasmic small interfering RNAs (siRNAs) enter the RNA-induced silencing complex and one strand guides cleavage of the target RNA by the Argonaute 2 protein1-3. A significant concern when applying siRNAs or expressing small hairpin RNAs (shRNAs) in human cells is activation of the Interferon (IFN) response4-10. Synthetic siRNAs harboring certain motifs can induce an immune response when delivered to mouse and human immune cells such as peripheral blood mononuclear cells, monocytes, plasmacytoid dendritic cells (pDCs) and nonplasmacytoid dendritic cells (mDCs)11-13. In the present study we have tested the immunostimulatory effects of lipid-delivered siRNAs versus Pol III promoter-expressed shRNAs in primary CD34+ progenitor-derived hematopoietic cells. We show that in this system, lipid-delivered siRNAs are potent inducers of IFNα and type I IFN gene expression, whereas the same sequences when expressed endogenously are nonimmunostimulatory.

Original languageEnglish
Pages (from-to)566-571
Number of pages6
JournalNature Biotechnology
Volume24
Issue number5
DOIs
StatePublished - May 2006

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