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Overcoming the challenge of delivering mRNA to extrahepatic tissues, especially specific cells within tissues, is crucial for precision therapy. In this study, a platform is developed for selective mRNA delivery to desired cells within tissues by combining lipid nanoparticle (LNP)\u2010based targeted delivery with mRNA sequence\u2010controlled expression. Through systematic optimization, a three\u2010component LNP platform is developed, enabling targeted mRNA delivery to the lung, liver, and spleen. The incorporation of unique microRNA target sites into the mRNA scaffold further enhances control over protein translation in specific cells within the target tissue. This combined strategy, named SELECT (Simplified LNP with Engineered mRNA for Cell\u2010type Targeting), demonstrates its efficacy in distinguishing mRNA expression between tumor and normal cells based on intracellular microRNA abundance. SELECT encapsulating mRNA encoding a tumor\u2010specific cytotoxic protein, human ELANE, exhibits selective mRNA delivery to tumor lesions and significant inhibition of tumor growth in a mouse model of melanoma lung metastasis. Overall, SELECT has great potential as a new precision tumor treatment approach and also offers promising prospects for other mRNA therapies targeting specific cell types.<\/jats:p>","DOI":"10.1002\/adma.202409812","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T02:59:40Z","timestamp":1728615580000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Simplified Lipid Nanoparticles for Tissue\u2010 And Cell\u2010Targeted mRNA Delivery Facilitate Precision Tumor Therapy in a Lung Metastasis Mouse Model"],"prefix":"10.1002","volume":"36","author":[{"given":"Yuan","family":"Fei","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering College of Future Technology Peking University  Beijing 100871 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of 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