Evidence map›Paper›PMID 39814992›Full record

ArticleNature chemical biology2025

PROTAR Vaccine 2.0 generates influenza vaccines by degrading multiple viral proteins.

Chunhe Zhang, Jihuan Hou, Zhen Li, Quan Shen, Haiqing Bai, Li Chen, Jinying Shen, Ping Wang, Yinlei Su, Jing Li and 11 more

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
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  4. Attenuation of Influenza a Virus into Live Vaccines Through C-End Degrons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Chunhe Zhang *State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Jihuan Hou *State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Zhen Li *State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Quan Shen *State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Haiqing Bai *Xellar Biosystems, Boston, MA, USA.
Li Chen *State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Jinying Shen *State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Ping Wang *State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Yinlei SuState Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Jing LiState Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Qisi ZhangState Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Chengyao LiuState Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Xuetong XiState Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Fei QiState Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.ORCID http://orcid.org/0000-0003-0122-3858
Yuting ChenState Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Xin XieXellar Biosystems, Boston, MA, USA.
Adam Yongxin YeDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Xiaoheng LiuInstitute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0001-9267-6339
Roberto PlebaniCenter for Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy.
George ChurchDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Longlong SiState Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. ll.si@siat.ac.cn.ORCID http://orcid.org/0000-0002-0504-1659

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82273837Shenzhen Science and Technology Innovation Commission JCYJ20220818101405011
6 · The paper itself

Abstract

Manipulating viral protein stability using the cellular ubiquitin-proteasome system (UPS) represents a promising approach for developing live-attenuated vaccines. The first-generation proteolysis-targeting (PROTAR) vaccine had limitations, as it incorporates proteasome-targeting degrons (PTDs) at only the terminal ends of viral proteins, potentially restricting its broad application. Here we developed the next-generation PROTAR vaccine approach, referred to as PROTAR 2.0, which enabled flexible incorporation of PTDs at various genomic loci of influenza viruses, including internal regions and terminal ends. The PROTAR 2.0 influenza viruses maintained efficient replication in UPS-deficient cells for large-scale production but were attenuated by PTD-mediated proteasomal degradation of viral proteins in conventional cells. Incorporation of multiple PTDs into one virus generated optimized PROTAR 2.0 vaccine candidates. In animal models, PROTAR 2.0 vaccine candidates were highly attenuated and a single-dose intranasal immunization induced robust and broad immune responses that provided complete cross-reactive protection against both homologous and heterologous viral challenges.

Indexed as

Influenza VaccinesViral ProteinsAnimalsDogsFemaleHumansMiceMice, Inbred BALB COrthomyxoviridae InfectionsProteasome Endopeptidase ComplexProteolysisUbiquitinVaccines, AttenuatedInfluenza VaccinesProteasome Endopeptidase ComplexUbiquitinVaccines, AttenuatedViral Proteins

Identifiers

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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.