Evidence map›Paper›PMID 39984501›Full record

ArticleNature communications2025

Oral delivery of therapeutic proteins by engineered bacterial type zero secretion system.

Xu Gong, Shan Liu, Bozhang Xia, Yichen Wan, Shuyi Zhang, Baoyan Zhang, Zehao Wang, Junge Chen, Fei Xiao, Xing-Jie Liang and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing 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

20 citing papers in PubMed.

  1. Review
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  4. Article
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  8. Engineering Microbial Particles for Next-Generation Biomedical Platforms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  9. Article
  10. Review
  11. Article
  12. Engineered Bacteria-Vesicle Delivered Lactate Reprogramming Boosts Tumor Radiosensitivity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
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  20. Review
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

11 authors.

Xu GongBeijing Advanced Innovation Center for Biomedical Engineering, School of Medical Science and Engineering, Beihang University, Beijing, P. R. China.
Shan LiuBeijing Advanced Innovation Center for Biomedical Engineering, School of Medical Science and Engineering, Beihang University, Beijing, P. R. China.
Bozhang XiaChinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, P. R. China.
Yichen WanBeijing Advanced Innovation Center for Biomedical Engineering, School of Medical Science and Engineering, Beihang University, Beijing, P. R. China.
Shuyi ZhangSchool of Pharmaceutical Sciences, Tsinghua University, Beijing, P. R. China.ORCID http://orcid.org/0000-0001-8500-5836
Baoyan ZhangBeijing Advanced Innovation Center for Biomedical Engineering, School of Medical Science and Engineering, Beihang University, Beijing, P. R. China.
Zehao WangBeijing Advanced Innovation Center for Biomedical Engineering, School of Medical Science and Engineering, Beihang University, Beijing, P. R. China.
Junge ChenBeijing Advanced Innovation Center for Biomedical Engineering, School of Medical Science and Engineering, Beihang University, Beijing, P. R. China.
Fei XiaoDepartment of Thoracic Surgery, China-Japan Friendship Hospital, Beijing, P. R. China. shawbjmu@163.com.ORCID http://orcid.org/0000-0003-2579-1809
Xing-Jie LiangChinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, P. R. China. liangxj@nanoctr.cn.ORCID http://orcid.org/0000-0002-4793-1705
Yun YangBeijing Advanced Innovation Center for Biomedical Engineering, School of Medical Science and Engineering, Beihang University, Beijing, P. R. China. yangyun0731@buaa.edu.cn.ORCID http://orcid.org/0000-0003-4287-4091

Funding

National Natural Science Foundation of China (National Science Foundation of China) No. 31900069National Natural Science Foundation of China (National Science Foundation of China) No. 82202336
6 · The paper itself

Abstract

Genetically engineered commensal bacteria are promising living drugs, however, their therapeutic molecules are frequently confined to their colonization sites. Herein, we report an oral protein delivery technology utilizing an engineered bacterial type zero secretion system (T0SS) via outer membrane vesicles (OMVs). We find that OMVs produced in situ by Escherichia coli Nissle 1917 (EcN) can penetrate the intact gut epithelial barrier to enter the circulation and that epithelial transcytosis involves pinocytosis and dynamin-dependent pathways. EcN is engineered to endogenously load various enzymes into OMVs, and the secreted enzyme-loaded OMVs are able to stably catalyze diverse detoxification reactions against digestive fluid and even enter the circulation. Using hyperuricemic mice and uricase delivery as a demonstration, we demonstrate that the therapeutic efficacy of our engineered EcN with a modified T0SS outperforms that with a direct protein secretion apparatus. The enzyme-loaded OMVs also effectively detoxify human serum samples, highlighting the potential for the clinical treatment of metabolic disorders.

Indexed as

Bacterial Secretion SystemsDrug Delivery SystemsEscherichia coliAdministration, OralAnimalsHumansMaleMiceTranscytosisBacterial Secretion Systems

Identifiers

PMID39984501
PMCPMC11845744

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.