Evidence map›Paper›PMID 42675166›Full record

ArticleNature biotechnology2026

Macropinocytosis-mediated recyclable LYTACs (McR-TACs) for receptor-independent protein degradation.

Peixin Liu, Yule Li, Tianyi Ma, Yawen You, Yu Chen, Michelle Y Cai, Quanyin Hu

Abstract read
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In one paragraph

Article in Nature biotechnology, 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. 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

7 authors.

Peixin LiuPharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-9417-5025
Yule LiPharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.
Tianyi MaPharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0009-0008-4847-9942
Yawen YouPharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.
Yu ChenPharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-9095-6609
Michelle Y CaiPharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.
Quanyin HuPharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA. qhu66@wisc.edu.ORCID http://orcid.org/0000-0003-2946-1655

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The degradation of cell membrane and extracellular proteins with lysosome-targeting chimeras (LYTACs) is limited by nonrecyclable, receptor-dependent mechanisms that shuttle proteins to lysosomes, restricting the broad use of this emerging technology. Here we developed a recyclable chimera composed of a polyzwitterion and protein of interest (POI) ligand for protein degradation. This chimera could interact with the cell membrane to trigger macropinocytosis together with the POI in a receptor-independent manner. Furthermore, it can dissociate from the POI in the acidic endocytic compartments and subsequently be exocytosed through the endoplasmic reticulum-Golgi transcytosis pathway. Ultimately, the exocytotic chimera initiates the next round of targeted protein degradation. These macropinocytosis-mediated recyclable LYTACs (McR-TACs) durably degrade the cell membrane protein (programmed cell death ligand 1) or the extracellular protein (macrophage migration inhibitory factor) in a triple-negative breast cancer mouse model, thereby inhibiting the tumor growth. Collectively, McR-TACs show the potential of leveraging natural transport pathways to create recyclable protein degraders with wide-ranging applications.

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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.