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Related Experiment Video

Updated: Sep 2, 2025

An Ecdysone Receptor-based Singular Gene Switch for Deliberate Expression of Transgene with Robustness, Reversibility, and Negligible Leakiness

An Ecdysone Receptor-based Singular Gene Switch for Deliberate Expression of Transgene with Robustness, Reversibility, and Negligible Leakiness

Published on: May 7, 2018

Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes.

Baylee J Russell¹, Steven D Brown¹, Nicole Siguenza¹

¹Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.

|August 5, 2022

Summary

This summary is machine-generated.

Engineered native bacteria can colonize the gut, providing lasting therapeutic benefits. This approach enables live bacterial therapeutics (LBTs) to reverse disease by delivering specific functions directly to the host microbiome.

Keywords:

bile acid metabolism complex gut microbiome glucose homeostasis gut microbiome metabolism microbe-host intereractions non-model gut microbes precision microbiome modulation synthetic biology type 2 diabetes

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Area of Science:

Microbiome research
Bacterial therapeutics
Host-microbe interactions

Background:

Live bacterial therapeutics (LBTs) aim to restore gut health by engrafting beneficial microbes.
Engineered microbes often fail to colonize the challenging gut environment in conventionally raised (CR) hosts.
Developing effective LBTs requires overcoming colonization barriers in the host gut.

Purpose of the Study:

To investigate the use of native bacteria as chassis for delivering therapeutic functions to the gut microbiome.
To demonstrate the feasibility of engineering native Escherichia coli for persistent engraftment and functional impact in CR hosts.
To establish a proof-of-concept for LBTs with curative intent utilizing native bacterial chassis.

Main Methods:

Isolation and modification of native Escherichia coli strains from conventionally raised (CR) mice.
Engineering these native E. coli strains to express specific functional genes for therapeutic purposes.
Administration of engineered native E. coli to CR hosts to assess engraftment and physiological effects.

Main Results:

Engineered native E. coli strains achieved perpetual engraftment in the host intestine.
The reintroduction of modified native bacteria induced lasting functional changes in CR host physiology.
These engineered native bacteria reversed pathology in CR hosts months after administration.

Conclusions:

Native bacteria serve as effective chassis for transgene delivery, overcoming colonization challenges in CR hosts.
This strategy enables the development of live bacterial therapeutics (LBTs) capable of inducing sustained beneficial functions.
The approach facilitates mechanistic studies of microbial functions and offers a path toward LBTs with curative potential.