Evidence map›Paper›PMID 41883582›Full record

ArticleMolecular therapy. Nucleic acids2026

A transferable SARS-CoV-2 IRES module enables dual translation initiation for enhanced antigen expression in COVID-19 mRNA vaccines.

Han Young Seo, Haewon Jung, Se-Young Lee, Hae-Gwang Jung, Hee Cho, Yu-Min Son, Yeonju Bak, Seo-Yeon Hwang, Jung-Hee Kim, In Ho Park and 2 more

Abstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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

1 citing paper in PubMed.

  1. Article
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

12 authors.

Han Young SeoDepartment of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
Haewon JungDepartment of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
Se-Young LeeDepartment of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
Hae-Gwang JungDepartment of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
Hee ChoDepartment of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
Yu-Min SonDepartment of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
Yeonju BakDepartment of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
Seo-Yeon HwangDepartment of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
Jung-Hee KimRpexBio Inc., 117-3, Hoegi-ro, Dongdaemun-gu, Seoul Biohub Global Center, Seoul 02455, Republic of Korea.
In Ho ParkDepartment of Biomedical Sciences, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Jeon-Soo ShinDepartment of Biomedical Sciences, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Jong-Won OhDepartment of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

mRNA vaccines are a versatile platform for infectious disease prevention and therapeutic applications, yet their performance is limited by exclusive reliance on cap-dependent translation, which is markedly suppressed under hypoxia and cellular stress. Here, we report a hybrid 5' untranslated region (5'UTR) that enables dual translation initiation via both cap-dependent and internal ribosome entry site (IRES) mechanisms. This element integrates a minimal stem-loop 4.5-5 module (SL4.5-5) from the SARS-CoV-2 genomic 5'UTR, in which a conserved 5'-UUUCGU-3' motif within the SL5 loops is essential for function. Incorporating the SL4.5-5 module downstream of conventional 5'UTRs confers cap-independent translation capacity and enhances overall translation efficiency under translation-restrictive conditions such as hypoxia. When applied to the 5'UTRs of clinically validated COVID-19 vaccines, this module improves antigen expression in both modified and unmodified mRNAs. Notably, unmodified Omicron BA.5 and XBB.1.5 mRNA vaccines containing this element elicited potent humoral and cellular immune responses at sub-microgram doses, comparable to those induced by the approved N1-methylpseudouridine-incorporated mRNA vaccine, raxtozinameran. These findings identify SL4.5-5 as a modular IRES element that enables dual translation initiation, promoting efficient protein synthesis under cap-dependent translation-restrictive conditions and expanding the functional landscape of mRNA vaccines and therapeutics beyond cap-dependent limitations.

Indexed as

4E-BP1BNT162b2 raxtozinamerancap-independent translationdual translation initiationhybrid 5′UTRhypoxia resistanceIRESmRNA vaccineMT: Clinical ApplicationsSARS-CoV-2 SL4.5–5

Identifiers

PMID41883582
PMCPMC13010108

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.