{
  "abstract": "Nonsense mutations in tumour suppressor genes (TSGs) drive cancer initiation and progression but remain “undruggable” due to formidable challenges in rescuing the functional impairment of heterogeneous truncated proteins with a single agent. Here we observe that suppressor transfer RNAs (sup-tRNAs) can overcome diverse nonsense mutations in TP53 , restoring full-length p53 expression and function. Sup-tRNAs enable high-fidelity incorporation of optimal amino acids and can further enhance the transcriptional activity of p53 to suppress tumour cell proliferation. Moreover, we employ a computational model to guide sup-tRNA design by in silico saturation mutagenesis for targeted readthrough of different nonsense-mutant TSGs. Remarkably, sup-tRNAs produced p53 variants with enhanced activity relative to restored wild-type p53, reducing cancer cell colony area by up to 82%. In two xenograft models harbouring nonsense mutant TP53 , we observed up to a 74% reduction in tumour volume after lipid nanoparticle (LNP)-based sup-tRNA treatment, attributed to robust recovery of p53 expression and function. Critically, sup-tRNA monotherapy surpassed nab-paclitaxel chemotherapy in efficacy, and their combination induced near-complete tumour regression (a maximum of 93% reduction in tumour volume) without detectable toxicity in multiple mouse tumour models. Our findings highlight the potential of tRNA-based therapy to provide a promising strategy for rescuing nonsense-mutant TP53 .",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "Bangyan Kong"
    },
    {
      "name": "Zhetao Zheng",
      "orcid": "0000-0002-8383-3010"
    },
    {
      "name": "Zeyuan Mi"
    },
    {
      "name": "Zhiyang Dou"
    },
    {
      "name": "Yuelin Yang"
    },
    {
      "name": "Yuxuan Shen"
    },
    {
      "name": "Liangzhen Dong",
      "orcid": "0009-0007-6634-5502"
    },
    {
      "name": "Jingru Lv"
    },
    {
      "name": "Ying Li"
    },
    {
      "name": "Qing Liang"
    },
    {
      "name": "Songlin Tian"
    },
    {
      "name": "Qing Xia",
      "orcid": "0000-0002-8191-7712"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7ngjs9692r28d.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-78578-7",
  "fulltext_url": null,
  "id": "7ngjs9692r28d",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-78578-7",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|RNA and protein synthesis mechanisms"
    ]
  ],
  "openalex": "W7223399745",
  "pdf_url": "https://www.nature.com/articles/s41467-026-78578-7_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/7ngjs9692r28d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:39Z",
      "native_id": "10.1038/s41467-026-78578-7",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41467-026-78578-7"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA and protein synthesis mechanisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Suppressor tRNAs restore functionally enhanced tumour suppressor protein to induce tumour regression",
  "title_text": "Suppressor tRNAs restore functionally enhanced tumour suppressor protein to induce tumour regression",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:39Z",
  "url": "https://research.draconitic.com/paper/7ngjs9692r28d",
  "venue": "Nature Communications",
  "versions": []
}