# Oral gene delivery targting distal ileocyte

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $381,250

## Abstract

It is aimed to develop a safe and effective oral gene delivery platform technology, taking advantage of the
physiological enterohepatic circulation to treat insulin-independent diabetes patients by systemically producing
an incretin, glucagon-like peptide 1 (GLP-1). The epithelial cells (enterocyte) in the gastrointestinal tract (GIT)
has a high turnover rate (~3.5 days) in humans, and the ileum is largely responsible for recycling free and
conjugated bile acids (collectively, BA) to the liver at a rate of 15-30 g/day with ~95% efficiency. We found that
nanoparticles can be actively absorbed through bile acid recycling pathways, though by altered mechanisms. It
is proposed in this grant application to leverage ileum enterocytes (ileocytes) as disposable protein factories,
which can be transfected by non-viral gene vectors in a selective manner via bile acid transporter-mediated
mechanisms, to supply systemic GLP-1. Selective transfection of the ileocyte would reduce exposure of the
internal organs to toxicity from cationic non-viral vectors and to potential permanent insertion mutations in long-
lasting cells in the body, while the continuous systemic supply of GLP-1 will be achieved by transfecting the
cells at a regular interval by oral administration. We intend in this study 1) to better understand the transport
pathways of anionic nanoparticles conjugated with BA, 2) to formulate an oral gene delivery system with a
unique anionic polymer that is safe and carries its own supply of the energy molecule, i.e., adenosine
triphosphate (ATP) to power transcription and translation, 3) to selectively target ileocytes by oral
administration of non-viral gene carriers and minimize the transport of the carriers into systemic circulation and
other internal organs, and 4) to treat type 2 diabetic animal models. The therapeutic output of twice-a-week
GLP-1 gene oral administration will be compared with twice-a-day injections of Exendin-4 (a GLP-1 receptor
agonist).

## Key facts

- **NIH application ID:** 9963248
- **Project number:** 5R01DK114015-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** You Han Bae
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963248

## Citation

> US National Institutes of Health, RePORTER application 9963248, Oral gene delivery targting distal ileocyte (5R01DK114015-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9963248. Licensed CC0.

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