# A Novel Recombinant Protein for Mitigating Acute Radiation Injury

> **NIH NIH R44** · THERASOURCE, LLC · 2021 · $974,383

## Abstract

PROJECT DESCRIPTION: This SBIR Phase II proposal is intended to further develop recombinant human
MFG-E8 (rhMFG-E8) as a radiation medical countermeasure (MCM) towards its approval by the FDA in the
future. Nuclear terrorism and major nuclear power plant leaks can cause acute radiation injury on a large
scale. Currently, there are limited drugs available to treat acute radiation syndrome (ARS). rhMFG-E8 is a
secretory glycoprotein that can maintain intestinal barrier homeostasis, enhance the clearance of dying cells,
and reduce inflammation. In our Phase I studies, we have shown that endogenous MFG-E8 is downregulated
after radiation injury, and treatment with E. coli-expressed His-tagged rhMFG-E8 improved the survival, body
weight, and intestinal integrity of rats exposed to gamma irradiation. However, E. coli-expressed His-tagged
proteins are inappropriate for the use in humans. Therefore, we have generated tag-free rhMFG-E8 using
human cells, significantly enhancing rhMFG-E8’s biological activities. We have shown that tag-free rhMFG-E8
significantly improved the survival, body weight, and intestinal integrity of mice exposed to X-ray irradiation.
We also determined rhMFG-E8’s pharmacokinetics, possible lack of mutagenicity, and short-term (3 months)
stability. Based on the above positive results, we hypothesize that human cell-expressed tag-free rhMFG-E8
can be developed as an effective and safe post-exposure mitigator of acute radiation injury. In this proposal,
we will assess tag-free rhMFG-E8’s efficacy as a radiation MCM in mice with the gastrointestinal acute
radiation syndrome (GI-ARS) and hematopoietic acute radiation syndrome (H-ARS). In addition, we will
determine the therapeutic window and effects of reduced treatment duration after radiation exposure, as well
as rhMFG-E8’s safety and potential oncogenicity and immunogenicity. These proposed studies should provide
crucial information on the efficacy and safety of rhMFG-E8 as a novel radiation MCM targeting GI-ARS and
combined GI- and H-ARS. Our ultimate goal is to obtain FDA approval to use rhMFG-E8 as a safe and
effective treatment for victims suffering from severe ARS.

## Key facts

- **NIH application ID:** 10133506
- **Project number:** 5R44AI114218-04
- **Recipient organization:** THERASOURCE, LLC
- **Principal Investigator:** Wayne Chaung
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $974,383
- **Award type:** 5
- **Project period:** 2014-06-10 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133506

## Citation

> US National Institutes of Health, RePORTER application 10133506, A Novel Recombinant Protein for Mitigating Acute Radiation Injury (5R44AI114218-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133506. Licensed CC0.

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