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In this study, we investigated the effects of oligonucleotide-gold nanoparticle conjugates (ON-GNPs) targeting\n                    <jats:italic>JAK2<\/jats:italic>\n                    or\n                    <jats:italic>JAK2<\/jats:italic>\n                    V617F mRNAs on nucleic acid-sensing pathways in HEL, SET2, and K562 cell lines. We evaluated changes in gene expression related to TLR9 and cGAS\/STING pathways, RAGE\/TLR9 receptor dynamics, and inflammatory cytokine release over short-term (0.5\u20132\u00a0h) and long-term (24\u201372\u00a0h) exposures. Our results demonstrated that ON-GNPs transiently suppressed\n                    <jats:italic>TLR9<\/jats:italic>\n                    ,\n                    <jats:italic>IRF7<\/jats:italic>\n                    , and\n                    <jats:italic>NFKB1<\/jats:italic>\n                    expression during the short term, followed by significant upregulation after 24\u00a0h, persisting up to 72\u00a0h. Notably,\n                    <jats:italic>JAK2<\/jats:italic>\n                    V617F-targeting ON-GNPs induced heightened\n                    <jats:italic>IRF7<\/jats:italic>\n                    activation in HEL and SET2 cells after 24\u00a0h without affecting TLR9\/RAGE expression. Additionally, IL-8 secretion increased in HEL and SET2 culture media after 72\u00a0h, correlating with interferon pathway activation. This study reveals that complementary ON-GNPs can modulate nucleic acid-sensing pathways, suppressing IL-8 and inflammatory signaling in the short term while inducing delayed activation of\n                    <jats:italic>TLR9<\/jats:italic>\n                    and\n                    <jats:italic>IRF7<\/jats:italic>\n                    in the presence of\n                    <jats:italic>JAK2<\/jats:italic>\n                    V617F. These findings provide a promising foundation for developing ON-GNP-based therapeutic strategies to manage inflammation and disease progression in Ph-MPNs.\n                  <\/jats:p>","DOI":"10.1007\/s00251-025-01374-y","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T21:50:55Z","timestamp":1740693055000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Suppressed activation of the IRF7 and TLR9 by JAK2V617F gold nanoparticles"],"prefix":"10.1007","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9034-8841","authenticated-orcid":false,"given":"Berkay","family":"Tokcan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4884-5298","authenticated-orcid":false,"given":"Esra Nur","family":"Demirta\u015f","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5035-4048","authenticated-orcid":false,"given":"Sel\u00e7uk","family":"S\u00f6zer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"issue":"4","key":"1374_CR1","doi-asserted-by":"publisher","first-page":"zcac039","DOI":"10.1093\/narcan\/zcac039","volume":"4","author":"MJL Aitken","year":"2022","unstructured":"Aitken MJL, Malaney P, Zhang X, Herbrich SM, Chan L, Benitez O et al (2022) Heterogeneous nuclear ribonucleoprotein K is overexpressed in acute myeloid leukemia and causes myeloproliferation in mice via altered Runx1 splicing. 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