{
  "abstract": "Oral delivery of peptides and other biologics are limited by enzymatic degradation and poor intestinal permeability. We developed a Saccharomyces cerevisiae-based platform expressing pro-DALAP, a fusion precursor of a dual GLP-1/GIP receptor agonist. The construct incorporates maltose-binding protein, a GM1-binding peptide, a cell-penetrating peptide, furin cleavage sites, and an albumin-binding domain, designed to support peptide stability, epithelial uptake, proteolytic activation, and prolonged systemic exposure. CRISPR/Cas12a-mediated integration of three expression cassettes into a protease-deficient yeast strain yielded 4.05 {+/-} 0.31 mg pro-DALAP/g dry biomass, compared with 1.27 {+/-} 0.21 mg/g in the single-copy strain, without detectable changes in cellular morphology or growth under the conditions evaluated. In vitro assays confirmed GM1 binding, furin-mediated processing, and activation of both GLP-1 and GIP receptors by DALAP. Preliminary intravenous toxicology studies in rats identified no treatment-related adverse findings at doses up to 300 {micro}g/kg/day for seven days. A 12-week, open-label, randomized controlled trial evaluated enteric-coated capsules containing lyophilized yeast expressing pro-DALAP against dietary guidance alone. The baseline cohort comprised 98 generally healthy adults who were overweight. An exploratory interim week-8 analysis involving eight participants per group showed numerically greater reductions in body weight (-2.29% vs. +0.14%) and waist circumference (-6.34% vs. -2.32%) in the intervention group, although neither comparison was statistically significant. These larger numerical differences were not reproduced in the completed analysis. Over the 12-week study, the intervention group showed modest numerical reductions in body weight and waist circumference. At week 12, mean percentage changes from baseline in body weight were -0.76% in the intervention group and -0.27% in the control group; corresponding changes in waist circumference were -3.60% and -3.69%. These descriptive trends did not translate into statistically significant between-group differences for either outcome. HbA1c reduction favored the control group. Among 40 intervention-group survey respondents, 37 reported no side effects. These findings support yeast-based production and in vitro functionality of pro-DALAP and provide preliminary observations on safety and efficacy. Validated pharmacokinetic measurements and adequately powered, blinded, placebo-controlled trials with longer follow-up periods are needed to determine systemic exposure, and evaluate sustained benefits, potentially supporting future clinical applications.",
  "abstract_shown": true,
  "affiliations": [
    "BioDrive, Inc."
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "K.-C. Kwon"
    },
    {
      "name": "O. Gaidarenko"
    },
    {
      "name": "N. Chang"
    },
    {
      "name": "C. Henderson"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cn4tm07kwnten.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.22.26365662",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.22.26365662v1.full",
  "id": "cn4tm07kwnten",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.22.26365662v1",
  "language": null,
  "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": [
    [
      "medrxiv",
      "endocrinology"
    ],
    [
      "openalex",
      "3003|Advanced Drug Delivery Systems"
    ]
  ],
  "openalex": "W7223476680",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.22.26365662v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cn4tm07kwnten.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:38Z",
      "native_id": "10.64898/2026.10.22.26365662",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.22.26365662v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:endocrinology",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "A Yeast-Based Platform for Oral Delivery of a Dual GLP-1/GIP Receptor Agonist: Engineering and Preliminary Clinical Evaluation",
  "title_text": "A Yeast-Based Platform for Oral Delivery of a Dual GLP-1/GIP Receptor Agonist: Engineering and Preliminary Clinical Evaluation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:21:38Z",
  "url": "https://research.draconitic.com/paper/cn4tm07kwnten",
  "venue": "medRxiv",
  "versions": []
}