# The Chloroplast Expression System as a platform for orally bioavailable muscle therapeutics

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2020 · $168,576

## Abstract

ABSTRACT
Two of the major pathways targeted enhance the actions of insulin-like growth factor I (IGF-I), and inhibit the
anti-growth pathways of Myostatin/Gdf8 and its related family members. Several clinical trials have occurred
and/or are underway examining protein/antibody and gene therapy approaches. While these approaches may
provide potent regulation of these pathways, and potentially preserve functional muscle mass, no study to date
has developed an orally bioavailable compound that can promote muscle growth. Thus, we assert that a major
challenge for delivery of pro-growth compounds is the lack of oral bioavailability, as all current options rely on
intramuscular or intravenous/arterial injections. In this application, we propose to capitalize on the oral
biovailability and stability of chloroplast bioencapsulation to produce myostatin propeptide and IGF-I, which
enable high production of protein relative to the total soluble protein in plants. The collaborative team will
combine expertise in chloroplast expression with expertise in skeletal muscle physiology to determine if a novel
delivery strategy for growth promoting agents can increase functional muscle mass in mice.
In Aim 1, the murine myostatin propeptide fused to the Fc domain of IgG will be expressed in Nicotiana
benthamiana and evaluated for cell-based activity and in vivo efficacy of myostatin inhibition. Likewise, in Aim
2, a similar construct of Pro-IGF-I-Fc will be made, and also tested in the same manner. At the completion of
this project, a thorough evaluation of this strategy will be complete, and potentially at least 1 candidate will be
identified to move forward into production in lettuce, which is a platform that is clinically relevant and affords
marker free production of therapeutic proteins. Ultimately, the chloroplast expression system may be
established as a potential strategy to express and deliver established factors as well as newly discovered
proteins that can promote muscle growth.

## Key facts

- **NIH application ID:** 9904474
- **Project number:** 5R21AR074271-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Elisabeth R Barton
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $168,576
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9904474

## Citation

> US National Institutes of Health, RePORTER application 9904474, The Chloroplast Expression System as a platform for orally bioavailable muscle therapeutics (5R21AR074271-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9904474. Licensed CC0.

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