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In orthotopic models of glioblastoma, the antibody localized to areas adjacent to necrotic tumor cells and promoted animal survival in a manner that depended on T cells. Mechanistic studies revealed that antibody binding to nucleic acids activated the cytoplasmic pattern recognition receptor cyclic GMP-AMP synthase (cGAS), thereby stimulating immune signaling and cGAS-dependent cytotoxicity. Moreover, the autoantibody could carry and deliver functional RNA into tumor, brain, and muscle tissues in live mice when administered locally. The findings establish a collaborative autoantibody\u2013nucleic acid interaction that is translatable to strategies for nonviral gene delivery and immunotherapy.<\/jats:p>","DOI":"10.1126\/scisignal.adk3320","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T18:09:23Z","timestamp":1742926163000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["A lupus-derived autoantibody that binds to intracellular RNA activates cGAS-mediated tumor immunity and can deliver RNA into cells"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8762-233X","authenticated-orcid":true,"given":"Xiaoyong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4916-8125","authenticated-orcid":true,"given":"Xiangjun","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0911-881X","authenticated-orcid":true,"given":"Benedette J.","family":"Cuffari","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5385-1496","authenticated-orcid":true,"given":"Fei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0190-527X","authenticated-orcid":true,"given":"Xingchun","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouqi","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip W.","family":"Noble","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6519-4999","authenticated-orcid":true,"given":"Melissa R.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA."},{"name":"Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3948-321X","authenticated-orcid":true,"given":"Olivia M.","family":"Turk","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupama","family":"Shirali","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2908-6894","authenticated-orcid":true,"given":"Joseph","family":"Gera","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA."},{"name":"Johnson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA."},{"name":"Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA."},{"name":"Department of Research &amp; 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