Enhanced Intracellular Stability and Translation Efficiency of mRNA Drugs by a 2-arm mRNA Platform.

Xucong Teng, Jiahao Lin, Qiushuang Zhang, Xiangdong Zhang, Yicong Dai, Jinghong Li

Abstract read

In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

6 authors.

Xucong TengCenter for BioAnalytical Chemistry, Hefei National Laboratory of Physical Science at Microscale, University of Science and Technology of China, Hefei, China.ORCID https://orcid.org/0000-0002-1514-0562

Jiahao LinCenter for BioAnalytical Chemistry, Hefei National Laboratory of Physical Science at Microscale, University of Science and Technology of China, Hefei, China.

Qiushuang ZhangNew Cornerstone Science Laboratory, Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University, Beijing, China.

Xiangdong ZhangNew Cornerstone Science Laboratory, Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University, Beijing, China.

Yicong DaiCenter for BioAnalytical Chemistry, Hefei National Laboratory of Physical Science at Microscale, University of Science and Technology of China, Hefei, China.

Jinghong LiCenter for BioAnalytical Chemistry, Hefei National Laboratory of Physical Science at Microscale, University of Science and Technology of China, Hefei, China.ORCID https://orcid.org/0000-0002-0750-7352

Funding

Beijing Life Science Academy Initiative Scientific Research Program 2024101RPIA02Fundamental Research Funds for the Central Universities WK9990250175Natural Science Foundation of Anhui Province 2508085QH286Natural Science Foundation of China 22504136New Cornerstone Science Foundation

6 · The paper itself

Abstract

The poly(A) tail deadenylation and transient protein expression of messenger RNA (mRNA) extremely hinder its therapeutic potential in genetic diseases, from which it follows that improving RNA stability and translation efficiency has emerged as a critical priority. In this study, we construct a 2-arm mRNA via a streamlined modular assembly approach, characterized by a unique topology formed through the dimerization of two mRNA 3' poly(A) tails. This distinctive architecture exhibits the capacity for efficiently recruiting poly(A)-binding proteins (PABPs) to activate the eIF3-eIF4F complex and promote highly efficient cap-dependent translation, markedly improving 3' tail stability and resistance to nuclease degradation, with an intracellular half-life of up to 65 h. Furthermore, the 2-arm mRNA sustains higher-level 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-arm mRNA platform that substantially enhances the translation capacity of mRNA, broadening its potential applications in mRNA-based therapeutics, particularly for the treatment of genetic disorders.

Indexed as

Protein BiosynthesisRNA, MessengerRNA StabilityAnimalsHumansMiceRNA, Messenger2‐arm mRNAdendritic mRNAmRNA stabilitymRNA therapyprolonged protein expression

Identifiers

PMID41955490

DOI10.1002/advs.75244

PMCPMC13334632

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LicenceCC BY

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.