{
  "abstract": "Oligonucleotide therapeutics hold transformative potential, yet their clinical translation is hindered by delivery barriers, including rapid renal/hepatic clearance and poor organ specificity. Bottlebrush polymer conjugates have emerged as a promising vector to address these limitations, but conventional architectures with uniform backbones can only achieve an unmodifiable, rigid biodistribution profile. Here, we report a library of sequence-defined \"digital\" bottlebrush polymers, precisely engineered with controlled placements of chemical motifs that modify physicochemical properties─including lipids, cholesterol, and cationic groups─along a polyphosphodiester backbone. Systematic evaluation of the digital bottlebrush polymer library reveals distinct structure-property relationships and enables organ-biased systemic delivery to several traditionally difficult-to-reach tissues, including muscle and skin. In a mouse model of rheumatoid arthritis, a single dose of a spleen-homing polymer-conjugated antisense oligonucleotide targeting TNF-α significantly reduced arthritis severity and preserved animal body weight. These findings establish a versatile design framework for tailoring bottlebrush polymers to specific therapeutic applications.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts02115, United States.",
    "Department of Chemical Engineering, Northeastern University, Boston, Massachusetts02115, United States.",
    "Department of Bioengineering, Northeastern University, Boston, Massachusetts02115, United States.",
    "Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts02215, United States."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jiachen Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Tingyu Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Yun Wei",
      "orcid": "0009-0002-2886-6503"
    },
    {
      "affs": [
        0
      ],
      "name": "Chenyang Xue"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiaming Xu",
      "orcid": "0000-0002-4373-5723"
    },
    {
      "affs": [
        0
      ],
      "name": "Guobin Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Peiru Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuyan Wang"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Shaobo Yang",
      "orcid": "0009-0006-5257-6775"
    },
    {
      "affs": [
        0
      ],
      "name": "Chloe Cavazos"
    },
    {
      "affs": [
        0
      ],
      "name": "Caroline Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "Allison Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Alex Wang"
    },
    {
      "affs": [
        0,
        2,
        1
      ],
      "name": "Ke Zhang",
      "orcid": "0000-0002-8142-6702"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7bn2azk8jv45b.bib",
  "cited_by": 0,
  "doi": "10.1021/jacs.6c09537",
  "fulltext_url": "https://europepmc.org/articles/PMC13587663",
  "id": "7bn2azk8jv45b",
  "issns": [
    "0002-7863",
    "1520-5126"
  ],
  "landing_url": "https://europepmc.org/article/MED/42915543",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|RNA Interference and Gene Delivery"
    ]
  ],
  "openalex": "W7161058854",
  "pdf_url": "https://europepmc.org/articles/PMC13587663?pdf=render",
  "pmcid": "PMC13587663",
  "pmid": "42915543",
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7bn2azk8jv45b.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42915543",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42915543"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA Interference and Gene Delivery",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Sequence-defined Digital Bottlebrush Polymers for Programmable Oligonucleotide Delivery.",
  "title_text": "Sequence-defined Digital Bottlebrush Polymers for Programmable Oligonucleotide Delivery.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/7bn2azk8jv45b",
  "venue": "Journal of the American Chemical Society",
  "versions": []
}