{
  "abstract": "Targeted protein degradation harnesses endogenous cellular machinery to eliminate disease-causing proteins, yet achieving phenotype-specific degradation across diverse cell types remains challenging. Here we show that antibody-enriched biomolecular condensates formed by liquid–liquid phase separation function as intracellular protein degradation tools, combining cytosolic trafficking with direct proteasome recruitment for targeted substrate clearance. These nanoscale condensates incorporate a short proteasome-targeting motif into phase-separation precursors, preserve antibody activity, enable direct proteasome recruitment, and improve delivery uniformity. When loaded with a mutation-specific antibody, these condensates selectively degrade oncogenic KRAS G12V without affecting wild-type KRAS in heterozygous cells, and suppress tumor growth in a KRAS G12V xenograft model. This strategy provides a modular platform for intracellular protein degradation that can be readily adapted by exchanging antibodies, without requiring genetic modification of cellular system. Targeted protein degradation has huge potential, but phenotype-specific degradation remains a difficulty. Here, a phase-separation biomolecular condensates as an intracellular degradation agent is developed, combining antibody-guided recognition with direct proteasome recruitment to enable phenotype-selective protein clearance.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA",
    "International Institute for Nanotechnology, Northwestern University, Evanston, IL, USA",
    "Aiiso Yufeng Li Family Department of Chemical and NanoEngineering, University of California San Diego, San Diego, CA, USA",
    "Department of Chemistry, Weinberg College of Arts & Sciences, Northwestern University, Evanston, IL, USA",
    "The Northwestern University Atomic and Nanoscale Characterization Experimental (NUANCE) Center, Northwestern University, Evanston, IL, USA",
    "The Ken & Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA",
    "Robert H. Laurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA",
    "Biohub, Chicago, IL, USA. daniel.wang@czbiohub.org",
    "Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA. daniel.wang@czbiohub.org",
    "Biohub, Chicago, IL, USA. shana.kelley@northwestern.edu",
    "Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA. shana.kelley@northwestern.edu",
    "Department of Chemistry, Weinberg College of Arts & Sciences, Northwestern University, Evanston, IL, USA. shana.kelley@northwestern.edu",
    "International Institute for Nanotechnology, Northwestern University, Evanston, IL, USA. shana.kelley@northwestern.edu",
    "Robert H. Laurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. shana.kelley@northwestern.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Y Li",
      "orcid": "0000-0002-6087-7934"
    },
    {
      "affs": [
        2
      ],
      "name": "Zhicheng Jin",
      "orcid": "0000-0001-6072-7533"
    },
    {
      "affs": [
        0
      ],
      "name": "Sharif U. Ahmed"
    },
    {
      "affs": [
        3,
        1
      ],
      "name": "Jagotamoy Das",
      "orcid": "0000-0003-2724-1827"
    },
    {
      "affs": [
        4
      ],
      "name": "Reiner Bleher",
      "orcid": "0000-0003-0962-797X"
    },
    {
      "affs": [
        3
      ],
      "name": "Dingran Chang",
      "orcid": "0000-0002-3127-8668"
    },
    {
      "affs": [
        5
      ],
      "name": "Xiaozhou Yu",
      "orcid": "0009-0009-5748-5559"
    },
    {
      "affs": [
        3
      ],
      "name": "Connor D. Flynn",
      "orcid": "0000-0003-0297-0273"
    },
    {
      "affs": [
        2
      ],
      "name": "Jiajing Zhou",
      "orcid": "0000-0001-5203-4737"
    },
    {
      "affs": [
        4
      ],
      "name": "Xiaobing Hu",
      "orcid": "0000-0002-9233-8118"
    },
    {
      "affs": [
        0
      ],
      "name": "Kangfu Chen",
      "orcid": "0000-0002-5077-2223"
    },
    {
      "affs": [
        3
      ],
      "name": "Kimberly T. Riordan",
      "orcid": "0000-0002-0010-4454"
    },
    {
      "affs": [
        6
      ],
      "name": "Ranjit Atwal"
    },
    {
      "affs": [
        3
      ],
      "name": "Julia M. Mayes",
      "orcid": "0009-0005-5778-0022"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Zongjie Wang",
      "orcid": "0000-0001-9900-7197"
    },
    {
      "affs": [
        9,
        10,
        11,
        12,
        13
      ],
      "name": "Shana O. Kelley",
      "orcid": "0000-0003-3360-5359"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5tm8fks4d7zr8.bib",
  "cited_by": 11,
  "doi": "10.1038/s41467-026-72967-8",
  "fulltext_url": null,
  "id": "5tm8fks4d7zr8",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-72967-8",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Degradation and Inhibitors"
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  "openalex": "W7161035492",
  "pdf_url": null,
  "pmcid": "PMC13396499",
  "pmid": "42129171",
  "published": "2026-05-13",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/5tm8fks4d7zr8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
      "native_id": "W7161035492",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-72967-8"
    }
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Degradation and Inhibitors",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Biomolecular Condensates as Protein Degradation Tools for Intracellular Targets",
  "title_text": "Biomolecular Condensates as Protein Degradation Tools for Intracellular Targets",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:07Z",
  "url": "https://research.draconitic.com/paper/5tm8fks4d7zr8",
  "venue": "Nature Communications",
  "versions": []
}