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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.

Titel:	The STING-STAT6 pathway drives Cas9-induced host response in human monocytes.
Autor/in / Beteiligte Person:	Kang, R ; Zhu, S ; Zeh, H ; Tang, D
Zeitschrift:	Biochemical and biophysical research communications, Jg. 506 (2018-11-17), Heft 1, S. 278-283
Veröffentlichung:	<2002- >: San Diego, CA : Elsevier ; <i>Original Publication</i>: New York, Academic Press., 2018
Medientyp:	academicJournal
ISSN:	1090-2104 (electronic)
DOI:	10.1016/j.bbrc.2018.10.080
Schlagwort:	Bacterial Proteins pharmacology Host Microbial Interactions immunology Humans Inflammation chemically induced THP-1 Cells CRISPR-Associated Protein 9 pharmacology Inflammation immunology Membrane Proteins metabolism Monocytes immunology STAT6 Transcription Factor metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Biochem Biophys Res Commun] 2018 Nov 17; Vol. 506 (1), pp. 278-283. <i>Date of Electronic Publication: </i>2018 Oct 20. MeSH Terms: CRISPR-Associated Protein 9 / pharmacology ; Inflammation / immunology ; Membrane Proteins / metabolism ; Monocytes / immunology ; STAT6 Transcription Factor / *metabolism ; Bacterial Proteins / pharmacology ; Host Microbial Interactions / immunology ; Humans ; Inflammation / chemically induced ; THP-1 Cells Comments: Comment in: Biochem Biophys Res Commun. 2019 Dec 17;520(4):706-707. (PMID: 31761088) References: Gastroenterology. 2018 May;154(6):1822-1835.e2. (PMID: 29425920) ; Science. 2014 Nov 28;346(6213):1258096. (PMID: 25430774) ; Nat Rev Immunol. 2015 Dec;15(12):760-70. (PMID: 26603901) ; J Exp Med. 2018 May 7;215(5):1287-1299. (PMID: 29622565) ; Curr Biol. 2018 Aug 6;28(15):2388-2399.e5. (PMID: 30057310) ; Nat Med. 2018 Jul;24(7):927-930. (PMID: 29892067) ; Cell. 2011 Oct 14;147(2):436-46. (PMID: 22000020) ; Genome Res. 2014 Jan;24(1):132-41. (PMID: 24253446) ; Mol Cell. 2013 Jul 25;51(2):135-9. (PMID: 23870141) ; Science. 2018 Aug 31;361(6405):866-869. (PMID: 30166482) ; Hepatology. 2016 Aug;64(2):488-500. (PMID: 27015352) ; J Immunol. 2000 Jun 15;164(12):6621-32. (PMID: 10843722) ; Biochem Biophys Res Commun. 2016 Nov 25;480(4):602-607. (PMID: 27793671) ; Hepatology. 2016 Jan;63(1):173-84. (PMID: 26403645) ; Cell Rep. 2017 Dec 26;21(13):3873-3884. (PMID: 29281834) ; Science. 2007 Mar 23;315(5819):1709-12. (PMID: 17379808) ; Cancer Res. 2017 Apr 15;77(8):2064-2077. (PMID: 28130223) ; Nat Methods. 2013 Oct;10(10):957-63. (PMID: 24076990) ; Front Immunol. 2015 Oct 16;6:529. (PMID: 26528290) ; Sci Transl Med. 2017 Oct 18;9(412):. (PMID: 29046432) ; Genome Res. 2018 Feb 22;:. (PMID: 29472270) ; Immunol Rev. 2012 Sep;249(1):158-75. (PMID: 22889221) Grant Information: R01 CA160417 United States CA NCI NIH HHS; R01 CA211070 United States CA NCI NIH HHS; R01 GM115366 United States GM NIGMS NIH HHS Contributed Indexing: Keywords: Cas9; Cytokine; Host response; Monocytes; STAT6; STING Substance Nomenclature: 0 (Bacterial Proteins) ; 0 (Membrane Proteins) ; 0 (STAT6 Transcription Factor) ; 0 (STAT6 protein, human) ; 0 (STING1 protein, human) ; EC 3.1.- (CRISPR-Associated Protein 9) Entry Date(s): Date Created: 20181024 Date Completed: 20190521 Latest Revision: 20201214 Update Code: 20240513 PubMed Central ID: PMC6290677

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