The STING-STAT6 pathway drives Cas9-induced host response in human monocytes

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Cas9 (CRISPR associated protein 9) is an RNA-guided DNA endonuclease enzyme derived from Streptococcus that has been widely used for genome editing in a variety of organisms, including humans. Here, we report that exogenous Cas9 protein can elicit an inflammatory immune response through the release of MIP3α, CD40L, and MPO in primary human peripheral blood mononuclear cells and human monocytic cell lines (THP1). Inhibition of the STING-STAT6 pathway blocks Cas9-induced proinflammatory mediator release. These results suggest that targeting the STING-STAT6 axis may prevent host immune responses in human gene therapy with the CRISPR-Cas9 system.

Original languageEnglish (US)
Pages (from-to)278-283
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume506
Issue number1
DOIs
StatePublished - Nov 17 2018

Keywords

  • Cas9
  • Cytokine
  • Host response
  • Monocytes
  • STAT6
  • STING

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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