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RNA nanotechnology has emerged rapidly and received attention in the last few years because of its significant aptitude for therapies. Hence, the present study aimed to design, construct, and characterize a multifunctional (anti-miR-34a DNA aptamer-kidney targeted) RNA nanoparticle (RNPs) based on bacteriophage phi29 packaging RNA three-way junction (pRNA-3WJ), and then explore their in vivo toxicity and therapeutic potentials in mice model of CKD. After confirming the safety and specific targeting capability of the prepared core 3WJ (3WJ) and the therapeutic 3WJ (3WJ-Kapt\/anti-miR-34a) RNPs to renal tissue using healthy mice, CKD was induced in C57BL\/6 mice using adenine. CKD mice were treated with a single intravenous injection of 3WJ or 3WJ-Kapt\/anti-miR-34a. Every week, 5 mice of each group were selected randomly for sample collection for 4 weeks post-treatment. The anti-miR-34a 3WJ-RNPs have shown stability, safety, and efficacy in renal targeting using DNA aptamer, by targeting miR-34a in renal tissue, 3WJ-Kapt\/anti-miR-34a suppressed profibrotic gene expression and induced anti-fibrotic pathways\u2019 expression. Our present study provides preliminary and pioneering evidence for the promising treatment of renal fibrosis and CKD through targeting miR-34a in the renal tissue by 3WJ-RNPs.<\/jats:p>","DOI":"10.1038\/s41434-025-00544-7","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T19:12:53Z","timestamp":1749841973000},"page":"359-375","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Aptamer-targeted anti-miR RNA construct based on 3WJ as a new approach for the treatment of chronic kidney disease in an experimental model"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4993-415X","authenticated-orcid":false,"given":"Aisha H. 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