{
    "abstract": "Directed protein evolution is central to biomedical applications but faces challenges such as experimental complexity, inefficient multiproperty optimization, and local maxima traps. Although in silico methods that use protein language models (PLMs) can provide modeled fitness landscape guidance, they struggle to generalize across diverse protein families and map to protein activity. We present EVOLVEpro, a few-shot active learning framework that combines PLMs and regression models to rapidly improve protein activity. EVOLVEpro surpasses current methods, yielding up to 100-fold improvements in desired properties. We demonstrate its effectiveness across six proteins in RNA production, genome editing, and antibody binding applications. These results highlight the advantages of few-shot active learning with minimal experimental data over zero-shot predictions. EVOLVEpro opens new possibilities for artificial intelligence-guided protein engineering in biology and medicine.",
    "authors": [
        {
            "affiliation": "Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School, Boston, MA, USA.\nGene and Cell Therapy Institute Mass General Brigham, Cambridge, MA, USA.\nCenter for Virology and Vaccine Research Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, USA.\nDepartment of Bioengineering Massachusetts Institute of Technology, Cambridge, MA, USA.",
            "firstname": "Kaiyi",
            "initials": "K",
            "lastname": "Jiang"
        },
        {
            "affiliation": "Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School, Boston, MA, USA.\nGene and Cell Therapy Institute Mass General Brigham, Cambridge, MA, USA.\nCenter for Virology and Vaccine Research Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, USA.",
            "firstname": "Zhaoqing",
            "initials": "Z",
            "lastname": "Yan"
        },
        {
            "affiliation": "Whitehead Institute Massachusetts Institute of Technology, Cambridge, MA, USA.",
            "firstname": "Matteo",
            "initials": "M",
            "lastname": "Di Bernardo"
        },
        {
            "affiliation": "Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School, Boston, MA, USA.\nGene and Cell Therapy Institute Mass General Brigham, Cambridge, MA, USA.\nCenter for Virology and Vaccine Research Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, USA.",
            "firstname": "Samantha R",
            "initials": "SR",
            "lastname": "Sgrizzi"
        },
        {
            "affiliation": "Department of Dermatology and Allergology Kantonspital St. Gallen, St. Gallen, Switzerland.",
            "firstname": "Lukas",
            "initials": "L",
            "lastname": "Villiger"
        },
        {
            "affiliation": "Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School, Boston, MA, USA.\nGene and Cell Therapy Institute Mass General Brigham, Cambridge, MA, USA.\nCenter for Virology and Vaccine Research Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, USA.",
            "firstname": "Alisan",
            "initials": "A",
            "lastname": "Kayabolen"
        },
        {
            "affiliation": "Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology, Cambridge, MA, USA.",
            "firstname": "B J",
            "initials": "BJ",
            "lastname": "Kim"
        },
        {
            "affiliation": "Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School, Boston, MA, USA.\nGene and Cell Therapy Institute Mass General Brigham, Cambridge, MA, USA.\nCenter for Virology and Vaccine Research Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, USA.",
            "firstname": "Josephine K",
            "initials": "JK",
            "lastname": "Carscadden"
        },
        {
            "affiliation": "Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.",
            "firstname": "Masahiro",
            "initials": "M",
            "lastname": "Hiraizumi"
        },
        {
            "affiliation": "Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.\nStructural Biology Division, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, Japan.\nInamori Research Institute for Science, 620 Suiginya-cho, Shimogyo-ku, Kyoto, Japan.",
            "firstname": "Hiroshi",
            "initials": "H",
            "lastname": "Nishimasu"
        },
        {
            "affiliation": "Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School, Boston, MA, USA.\nGene and Cell Therapy Institute Mass General Brigham, Cambridge, MA, USA.\nCenter for Virology and Vaccine Research Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, USA.",
            "firstname": "Jonathan S",
            "initials": "JS",
            "lastname": "Gootenberg"
        },
        {
            "affiliation": "Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School, Boston, MA, USA.\nGene and Cell Therapy Institute Mass General Brigham, Cambridge, MA, USA.\nCenter for Virology and Vaccine Research Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, USA.",
            "firstname": "Omar O",
            "initials": "OO",
            "lastname": "Abudayyeh"
        }
    ],
    "conclusions": null,
    "copyrights": null,
    "doi": "10.1126/science.adr6006",
    "journal": "Science (New York, N.Y.)",
    "keywords": [],
    "methods": null,
    "publication_date": "2024-11-21",
    "pubmed_id": "39571002",
    "results": null,
    "title": "Rapid in silico directed evolution by a protein language model with EVOLVEpro.",
    "xml": "<Element 'PubmedArticle' at 0x788504915990>"
}