Evidence map›Paper›PMID 40229275›Full record

ArticleNature communications2025

Programmable protein stabilization with language model-derived peptide guides.

Lauren Hong, Tianzheng Ye, Tian Z Wang, Divya Srijay, Howard Liu, Lin Zhao, Rio Watson, Sophia Vincoff, Tianlai Chen, Kseniia Kholina and 3 more

Abstract read
PubMed Full text at PMC Publisher
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 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Lauren Hong *Department of Biomedical Engineering, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0002-1675-4806
Tianzheng Ye *Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0001-6678-7115
Tian Z Wang *Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Divya SrijayDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Howard LiuDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Lin ZhaoDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0002-1678-7763
Rio WatsonDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Sophia VincoffDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Tianlai ChenDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0003-0706-5731
Kseniia KholinaDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Shrey GoelDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Matthew P DeLisaRobert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, USA.
Pranam ChatterjeeDepartment of Biomedical Engineering, Duke University, Durham, NC, USA. pranam.chatterjee@duke.edu.ORCID http://orcid.org/0000-0003-3957-8478

Funding

Screening for Cys-Reactive Ligands to Target PAX3-FOXO1U54CA231630 · NCI · DUKE UNIVERSITY · PI COUNTER, CHRISTOPHER M, LINARDIC, CORINNE MARY · 2019 to 2023
$6.5M
Towards the Design of Programmable, Isoform-Selective Proteome Editing SystemR35GM155282 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Pranam Chatterjee · 2024 to 2026
$1.2M
Programmable peptide-guided protein degradationR21CA278468 · NCI · DUKE UNIVERSITY · PI CHATTERJEE, PRANAM · 2023 to 2023
$388k
NCI NIH HHS R21 CA278468NCI NIH HHS U54 CA231630NIGMS NIH HHS R35 GM155282
6 · The paper itself

Abstract

Dysregulated protein degradation via the ubiquitin-proteasomal pathway can induce numerous disease phenotypes, including cancer, neurodegeneration, and diabetes. While small molecule-based targeted protein degradation (TPD) and targeted protein stabilization (TPS) platforms can address this dysregulation, they rely on structured and stable binding pockets, which do not exist to classically "undruggable" targets. Here, we expand the TPS target space by engineering "deubiquibodies" (duAbs) via fusion of computationally-designed peptide binders to the catalytic domain of the potent OTUB1 deubiquitinase. In human cells, duAbs effectively stabilize exogenous and endogenous proteins in a DUB-dependent manner. Using protein language models to generate target-binding peptides, we engineer duAbs to conformationally diverse target proteins, including key tumor suppressor proteins p53 and WEE1, and heavily-disordered fusion oncoproteins, such as PAX3::FOXO1. We further encapsulate p53-targeting duAbs as mRNA in lipid nanoparticles and demonstrate effective intracellular delivery, p53 stabilization, and apoptosis activation, motivating further in vivo translation.

Indexed as

PeptidesApoptosisCatalytic DomainCell Cycle ProteinsDeubiquitinating EnzymesForkhead Box Protein O1HumansNanoparticlesProtein EngineeringProtein StabilityProtein-Tyrosine KinasesProteolysisTumor Suppressor Protein p53Cell Cycle ProteinsDeubiquitinating EnzymesForkhead Box Protein O1PeptidesProtein-Tyrosine KinasesTumor Suppressor Protein p53

Identifiers

PMID40229275
PMCPMC11997201

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.