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In this study, we construct a 2\u2010arm mRNA via a streamlined modular assembly approach, characterized by a unique topology formed through the dimerization of two mRNA 3\u2019 poly(A) tails. This distinctive architecture exhibits the capacity for efficiently recruiting poly(A)\u2010binding proteins (PABPs) to activate the eIF3\u2010eIF4F complex and promote highly efficient cap\u2010dependent translation, markedly improving 3\u2019 tail stability and resistance to nuclease degradation, with an intracellular half\u2010life of up to 65 h. Furthermore, the 2\u2010arm mRNA sustains higher\u2010level protein expression for over two weeks in protein replacement therapy of hemophilic mice compared to linear mRNA. In conclusion, this work presents a novel 2\u2010arm mRNA platform that substantially enhances the translation capacity of mRNA, broadening its potential applications in mRNA\u2010based therapeutics, particularly for the treatment of genetic disorders.<\/jats:p>","DOI":"10.1002\/advs.75244","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T19:12:42Z","timestamp":1775761962000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced Intracellular Stability and Translation Efficiency of mRNA Drugs by a 2\u2010arm mRNA Platform"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1514-0562","authenticated-orcid":false,"given":"Xucong","family":"Teng","sequence":"first","affiliation":[{"name":"Center for BioAnalytical Chemistry Hefei National Laboratory of Physical Science at Microscale University of Science and Technology of China  Hefei 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