# Engineering next generation probiotics for delivery of therapeutics

> **NIH NIH R43** · MEDOSOME BIOTEC, LLC · 2023 · $325,000

## Abstract

PROJECT SUMMARY / ABSTRACT
Peptide and protein drugs (PPDs) are potent therapeutics to treat a broad spectrum of diseases. Parenteral
administration is limited due to their poor bioavailability and stability. Oral delivery of PPDs faces additional
obstacles in the gastrointestinal tract. We have developed an innovative, probiotics-based platform technology
for the oral delivery of therapeutic PPDs that targets a number of challenging chronic diseases. This delivery
system is robust, highly efficient, cost effective, easy to administer and safe. Our recent published results provide
proof-of concept for the feasibility of using Lactobacillus as a live vector for the delivery of peptide and protein
with enhanced tissue bioavailability and efficacy. However, our current platform has several limitations for clinical
application, which include the use of an antibiotic gene as selection marker, plasmid segregation instability and
lack of built-in biocontainment strategy, which may raise safety concern with engineered microbes disseminated
into the environment. The goal of this project is to develop a next generation probiotics-based platform for the
delivery of peptide and protein therapeutics with more stable and effective biocontainment. Specifically, we will
(1) construct, characterize and validate an antibiotic-resistance-gene free, auxotrophic complementation-based
expression system to achieve stable and high-level expression of the therapeutic peptide in a probiotic strain of
L. paracasei; (2) develop and validate the efficacy and stability of inducible kill-switches for the biocontainment
of genetically engineered L. paracasei; and (3) validate the efficacy and stability of engineered probiotics
expressing the therapeutic peptide with a built-in inducible kill-switch in animal models. If successful, the platform
developed in this project with its modular design will be applicable to hundreds of probiotic Lactobacillus species
that have shown species-specific benefits, as well as to deliver other PPDs. This drug delivery system will be
applicable to numerous human diseases – many chronic and recalcitrant - from metabolic, cardiovascular and
immune dysfunction to aging and neurodegenerative diseases. It will also provide a powerful research tool to
modulate the structure and function of the gut microbiota, to further investigate the interplay of microbe-microbe
and host-microbe interactions, and elucidate the molecular mechanisms involved in the health-promoting effects
of these probiotics.

## Key facts

- **NIH application ID:** 10697438
- **Project number:** 1R43TR004525-01
- **Recipient organization:** MEDOSOME BIOTEC, LLC
- **Principal Investigator:** Richard Wagner
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $325,000
- **Award type:** 1
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10697438

## Citation

> US National Institutes of Health, RePORTER application 10697438, Engineering next generation probiotics for delivery of therapeutics (1R43TR004525-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10697438. Licensed CC0.

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