Evidence map›Paper›PMID 40340249›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

Intrinsic/proximal cell surface marker logic-gated extracellular targeted protein degradation in specific cell population.

Yafeng Wang, Guiquan Zhang, Ping Rong, Panpan Guo, Shisheng Huang, Yang Hang, Pei Wang, Lin Tang, Xiaojing Li, Xiaojun Tang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

14 authors.

Yafeng WangDepartment of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing 210008, China.
Guiquan ZhangThe Second People's Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou 213000, China; College of Life Sciences, Nanjing Medical University, Changzhou 213000, China.
Ping RongState Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center at Medical School of Nanjing University, Nanjing 210061, China.
Panpan GuoDepartment of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing 210008, China.
Shisheng HuangThe Second People's Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou 213000, China; College of Life Sciences, Nanjing Medical University, Changzhou 213000, China.
Yang HangDepartment of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing 210008, China.
Pei WangState Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center at Medical School of Nanjing University, Nanjing 210061, China.
Lin TangDepartment of Rheumatology and Immunology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China.
Xiaojing LiDepartment of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing 210008, China.
Xiaojun TangDepartment of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing 210008, China.
Shuai DingDepartment of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing 210008, China.
Xingxu HuangThe Second People's Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou 213000, China; Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; College of Life Sciences, Nanjing Medical University, Changzhou 213000, China.
Jianghuai LiuState Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center at Medical School of Nanjing University, Nanjing 210061, China. Electronic address: liujianghuai@nju.edu.cn.
Lingyun SunDepartment of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing 210008, China. Electronic address: lingyunsun@nju.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Molecular tether-mediated extracellular targeted protein degradation (eTPD) presents an innovative technology and underlies a promising drug modality. However, to precisely implement eTPD within specific cell compartments remains a significant challenge. As eTPD depends on the degrader molecule expression and activity, we first seek to expand the panel of potential eTPD degraders. To this end, more than 50 receptors with variable tissue distributions are screened for identification of those with substantial endocytic rates. We subsequently assemble the bispecific, "Selected endocytic carrier-targeting chimeras (SecTAC)," and validate their efficacies to program the target cells to internalize membrane/extracellular protein cargos (or nucleic acids). Moreover, administration of a SecTAC for removal of excessive immunoglobulin G via a currently validated, emerging degrader (CD71) leads to evident therapeutic effect in a mouse lupus model. To further enhance cell-targeting specificity, we next develop logic-gated eTPD (LOG-eTPD) based on a combination of chimeras that indirectly couple cargo and degrader via another cell surface gating marker. Particularly, we find that a selective surface marker from the neighboring cells also may be exploited as input for LOG-eTPD in a therapeutically relevant context. Taken together, the present work has laid a strong foundation for developing eTPD agents that combine high potency with precision and safety.

Indexed as

ProteolysisAnimalsBiomarkersDisease Models, AnimalEndocytosisHumansMiceBiomarkersbispecific antibodyendocytic degraderextracellular targeted protein degradationlogic gateselected endocytic carrier-targeting chimeratargeting specificity

Identifiers

PMID40340249
PMCPMC12461647

What OpenQuestion holds

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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.