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Updated: Feb 3, 2026

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages
Published on: April 6, 2022
The STING-STAT6 pathway drives Cas9-induced host response in human monocytes
Rui Kang1, Shan Zhu2, Herbert Zeh3
1The Third Affiliated Hospital, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 510510, China; Department of Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USA; Department of Surgery, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
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.
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