ArticleThe Journal of clinical investigation2023
Keratinocytes sense and eliminate CRISPR DNA through STING/IFN-κ activation and APOBEC3G induction.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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Who cites it
15 citing papers in PubMed, 16 citations in OpenAlex.
- Myeloid infiltration and epidermal dysregulation characterize cutaneous photosensitivity in systemic lupus erythematosus.Science translational medicine · 2026Article
- Insulin-regulated actin dynamics is disrupted in a human keratinocyte model of Hailey-Hailey disease.American journal of physiology. Cell physiology · 2026Article
- Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Insulin-Regulated Actin Dynamics is Disrupted in a Human Keratinocyte Model of Hailey Hailey Disease.bioRxiv : the preprint server for biology · 2025Article
- Mimicking the LOX-Related Autosomal Recessive Congenital Ichthyosis Skin Disease Using a CRISPR-Cas9 System and Unravelling 12S-LOX Function in the Skin.Dermatopathology (Basel, Switzerland) · 2025Article
- IgG autoantibodies in bullous pemphigoid induce a pathogenic MyD88-dependent pro-inflammatory response in keratinocytes.Nature communications · 2025Article
- HSPA2 influences the differentiation and production of immunomodulatory mediators in human immortalized epidermal keratinocyte lines.Cell death & disease · 2025Article
- Epidermal ZBP1 stabilizes mitochondrial Z-DNA to drive UV-induced IFN signaling in autoimmune photosensitivity.Science immunology · 2025Article
- Innate Immune Sensors and Cell Death-Frontiers Coordinating Homeostasis, Immunity, and Inflammation in Skin.Viruses · 2025Review
- Characterizing the immune infiltrate in secondary syphilis: implications for transmission and pathology.Frontiers in immunology · 2025Article
- APOBEC3B expression in 293T viral producer cells drives mutations in chimeric antigen receptors and reduces CAR T cell efficacy.Molecular therapy. Oncology · 2024Article
- HERC6 regulates STING activity in a sex-biased manner through modulation of LATS2/VGLL3 Hippo signaling.iScience · 2024Article
- Epidermal ZBP1 stabilizes mitochondrial Z-DNA to drive UV-induced IFN signaling in autoimmune photosensitivity.bioRxiv : the preprint server for biology · 2024Article
- A Critical Role for IFN-β Signaling for IFN-κ Induction in Keratinocytes.Frontiers in lupus · 2024Article
- Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
CRISPR/Cas9 has been proposed as a treatment for genetically inherited skin disorders. Here we report that CRISPR transfection activates STING-dependent antiviral responses in keratinocytes, resulting in heightened endogenous interferon (IFN) responses through induction of IFN-κ, leading to decreased plasmid stability secondary to induction of the cytidine deaminase gene APOBEC3G. Notably, CRISPR-generated KO keratinocytes had permanent suppression of IFN-κ and IFN-stimulated gene (ISG) expression, secondary to hypermethylation of the IFNK promoter region by the DNA methyltransferase DNMT3B. JAK inhibition via baricitinib prior to CRISPR transfection increased transfection efficiency, prevented IFNK promoter hypermethylation, and restored normal IFN-κ activity and ISG responses. This work shows that CRISPR-mediated gene correction alters antiviral responses in keratinocytes, has implications for future gene therapies for inherited skin diseases using CRISPR technology, and suggests pharmacologic JAK inhibition as a tool for facilitating and attenuating inadvertent selection effects in CRISPR/Cas9 therapeutic approaches.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.