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However, the efficacy of therapy targeting a single oncomiRNA (oncomiR) is limited, as multiple oncomiRs often act simultaneously in promoting CRC development. In addition, current anti\u2010miRNA nucleotide (AMiN) design faces challenges, including high synthetic error rate and difficulty in synthesizing long oligonucleotides. Circular single\u2010stranded DNA (CssDNA), an ancient form of DNA that has gained increasing attention recently, is known for its easy synthesis, high stability, low error rate, and long size potential. Here, we develop a multi\u2010oncomiR targeting platform with low immunogenicity, high stability and long\u2010size potential using in vivo M13 phage\u2010generated CssDNA. This CssDNA acts as a sponge, which attracts and degrades multiple abnormally overexpressed oncomiRs in CRC. The degradation of oncomiRs promotes the expression of tumor suppressor genes (TSGs), inhibiting CRC development. Further, the degradation of oncomiRs from the sponge releases the free CssDNA for second round of action, which results in the efficacy and recyclability of CssDNA. It's visible to spread this novel, sequence customizable, multi\u2010oncomiR targeting platform using CssDNA as a stable, low\u2010immunogenic and recyclable AMiN in antagonizing miRNA\u2010mediated repression of TSG expression for other tumor suppression.<\/jats:p>","DOI":"10.1002\/smtd.70720","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:20:23Z","timestamp":1778674823000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Programmable Circular Single\u2010Stranded DNA Acts as Recyclable Anti\u2010miRNA Nucleotides to Inhibit Colorectal Cancer"],"prefix":"10.1002","volume":"10","author":[{"given":"Jinghao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Science &amp; Technology of China  Hefei Anhui China"},{"name":"Hangzhou Institute of Medicine Chinese Academy of Sciences  Hangzhou Zhejiang 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