Evidence map›Paper›PMID 38519719›Full record

ArticleNature biotechnology2025

Branched chemically modified poly(A) tails enhance the translation capacity of mRNA.

Hongyu Chen, Dangliang Liu, Jianting Guo, Abhishek Aditham, Yiming Zhou, Jiakun Tian, Shuchen Luo, Jingyi Ren, Alvin Hsu, Jiahao Huang and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
22.9field-weighted citation impact, top 1% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

78 citing papers in PubMed, 98 citations in OpenAlex.

  1. Article
  2. Article
  3. Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026
    Review
  4. Review
  5. Circular Photocaged mRNA for Light-induced Late-stage Activation of Translation.Angewandte Chemie (International ed. in English) · 2026
    Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. DNA Flap-Mediated Control of Transcription for Programmable RNA Synthesis.Angewandte Chemie (International ed. in English) · 2026
    Article
  16. Article
  17. Review
  18. "More" Artificial mRNAs: Beyond the Art of Nature.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  19. Review
  20. Article

18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Hongyu ChenDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Dangliang LiuDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jianting GuoDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-5691-5707
Abhishek AdithamBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Yiming ZhouDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jiakun TianDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Shuchen LuoDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8754-1413
Jingyi RenDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Alvin HsuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jiahao HuangDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6349-9799
Franklin KostasDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Mingrui WuDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Xiao WangDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA. xwangx@mit.edu.ORCID http://orcid.org/0000-0002-3090-9894
Broad Institute · US

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
Single-cell in situ analysis of RNA modifications in intact tissuesDP2GM146245 · NIGMS · BROAD INSTITUTE, INC. · PI WANG, XIAO · 2021 to 2024
$2.4M
Expanding the Scope of Base EditingU01AI142756 · NIAID · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2018 to 2022
$2.1M
NHGRI NIH HHS RM1 HG009490NIAID NIH HHS U01 AI142756NIGMS NIH HHS DP2 GM146245NIGMS NIH HHS R35 GM118062U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) 1DP2GM146245-01
6 · The paper itself

Abstract

Although messenger RNA (mRNA) has proved effective as a vaccine, its potential as a general therapeutic modality is limited by its instability and low translation capacity. To increase the duration and level of protein expression from mRNA, we designed and synthesized topologically and chemically modified mRNAs with multiple synthetic poly(A) tails. Here we demonstrate that the optimized multitailed mRNA yielded ~4.7-19.5-fold higher luminescence signals than the control mRNA from 24 to 72 h post transfection in cellulo and 14 days detectable signal versus <7 days signal from the control in vivo. We further achieve efficient multiplexed genome editing of the clinically relevant genes Pcsk9 and Angptl3 in mouse liver at a minimal mRNA dosage. Taken together, these results provide a generalizable approach to synthesize capped branched mRNA with markedly enhanced translation capacity.

Indexed as

Poly AProtein BiosynthesisRNA, MessengerAnimalsGene EditingHumansLiverMiceProprotein Convertase 9Pcsk9 protein, mousePoly AProprotein Convertase 9RNA, Messenger

Identifiers

PMID38519719
PMCPMC11416571
OpenAlexW4393096890

What OpenQuestion holds

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Registered trials

None linked

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.