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

Biochem Biophys Res Commun. 2018 Nov 17;506(1):278-283. doi: 10.1016/j.bbrc.2018.10.080. Epub 2018 Oct 20.

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.

Keywords: Cas9; Cytokine; Host response; Monocytes; STAT6; STING.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / pharmacology
  • CRISPR-Associated Protein 9 / pharmacology*
  • Host Microbial Interactions / immunology
  • Humans
  • Inflammation / chemically induced
  • Inflammation / immunology*
  • Membrane Proteins / metabolism*
  • Monocytes / immunology*
  • STAT6 Transcription Factor / metabolism*
  • THP-1 Cells

Substances

  • Bacterial Proteins
  • Membrane Proteins
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • STING1 protein, human
  • CRISPR-Associated Protein 9