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Res Sq
ResearchSquare
Research Square
2693-5015
American Journal Experts

39184085
10.21203/rs.3.rs-4354377/v1
10.21203/rs.3.rs-4354377
preprint
1
Article
The Generation of an ocular anti-inflammatory biotherapeutic to enhance wound healing.
Leger Anthony St.
Shane Jackie
Evans Matthew
Rigas Yannis
Shanks Robert
16 8 2024
rs.3.rs-4354377https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
https://www.researchsquare.com/article/rs-4354377/v1
nihpp-rs4354377v1.pdf
Abstract

Microbes exist at and colonize mucosal surfaces striking a balance with the host immune system, so that these microbes can thrive on host tissues without causing pathology. Because of this, mucosal barrier-colonizing bacteria can be leveraged to act as long-term delivery vehicles for naturally derived therapeutics. Here, we use a mouse model of corneal wound healing to show that the eye-colonizing bacterium, Corynebacterium mastitidis (C. mast) can be engineered to produce and secrete bioactive murine anti-inflammatory interleukin (mIL)-10. Specifically, we used transposon mutagenesis to identify a native C. mast-specific secretion signal that was used to direct C. mast to secrete mIL-10. Mini-transposons were generated to deliver secretion capable mIL-10 to the bacterial genome. After screening, two isolates were identified that can: 1) colonize the eye, 2) produce and secrete mIL-10, and 3) enhance wound healing in an IL-10-dependent manner. This proof of concept illustrates that eye-colonizing bacteria can be engineered to deliver therapeutics to the ocular surface for the alleviation of ocular surface disease(s).
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