{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:05:52Z","timestamp":1785330352805,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Nucleic acid therapeutics offer unique opportunities to develop personalized precision therapies by responding specifically and effectively at the gene level to evolving pathogens. However, many nucleic acid drugs employ a single\u2010target strategy, which is effective in monogenic disorders, yet can be ineffective in treating diseases characterized by complex and interacting molecular events. Nucleic acid combinations capable of simultaneously modulating multiple pathways and harnessing concerted effects constitute a promising approach to combatting complex, dynamically evolving and heterogeneous diseases. Here, we report a combination strategy utilizing small activating RNA to activate tumor suppressor genes alongside small interfering RNA to silence oncogenes for therapeutic potential and clinical relevance in cancer treatment using patient\u2010derived tumor models of pancreatic cancer. Transcriptomic and proteomic profiling of individual patient tumors enabled rational design of patient\u2010specific combinations, which exhibited superior anticancer efficacy through coordinated regulation of multiple genes. Importantly, diverse combinations were tailored to individual patient tumor models to elicit therapeutic responses, while certain specific combinations demonstrated therapeutic efficacy across different tumor models that shared similar genetic features, highlighting the flexibility and pan\u2010treatment potential. Our findings not only confirm the efficacy of the combination approach for cancer treatment, but also underscore its potential applicability to other complex malignancies.<\/jats:p>","DOI":"10.1002\/advs.76840","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:28:00Z","timestamp":1785328080000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Concerted Action of Targeted Nucleic Acid Therapeutics as Flexible, Precision and Personalized Cancer Treatment"],"prefix":"10.1002","author":[{"given":"Jing","family":"Wu","sequence":"first","affiliation":[{"name":"Aix Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325 Equipe Labellis\u00e9e Ligue Contre le Cancer Marseille France"},{"name":"Aix Marseille University, CNRS, INSERM, Institut Paoli\u2010Calmettes CRCM Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Aix Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325 Equipe Labellis\u00e9e Ligue Contre le Cancer Marseille France"},{"name":"State Key Laboratory of Natural Medicines, Joint International Research Laboratory of Target Discovery and New Drug Innovation (Ministry of Education), Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdechakour","family":"Elkihel","sequence":"additional","affiliation":[{"name":"Aix Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325 Equipe Labellis\u00e9e Ligue Contre le Cancer Marseille 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