University of Pittsburgh researchers have developed an ocular live biotherapeutic product (LBP) by engineering eye-colonizing bacteria to continuously deliver therapeutic agents to eye wounds and promote healing. Corynebacterium mastitidis (C. mast) can infect the eyes of immunocompetent hosts without excessive inflammation or pathology (commensal infection). Using transposon mutagenesis, C. mast can be engineered to produce and secrete the bioactive anti-inflammatory interleukin IL-10. This first-of-a-kind bacterium can promote corneal wound healing and offers a novel therapeutic approach to deliver ocular therapeutics.
An eye-colonizing bacteria has been engineered to produce and secrete the cytokine IL-10. Inoculation of the eye with these engineered bacteria can promote the healing of corneal wounds.
Description
The cornea plays a crucial role in vision and in protecting the eye from dust, microbes, and other foreign material. Corneal wounds occur in hundreds of thousands of Americans each year. Corneal healing is a biologically complex process and too much inflammation in the cornea can result in failed or inefficient healing, leading to vision damage or even loss. There is a pressing clinical need to develop new strategies to promote corneal healing. The cornea is a mucosal surface with its own microbiome of nonpathogenic mucosal barrier-colonizing bacteria. This novel therapeutic approach uses these commensal bacteria to produce and secrete anti-inflammatory or other therapeutic compounds to the cornea.
Applications
• Corneal wound healing
• Drug delivery to mucosal membranes
Advantages
During the corneal wound healing process an immune response is mounted. This immune response can result in upregulation of inflammatory cytokines known to suppress signal transducer and activator of transcription 3 (STAT3) activity, disrupting normal wound healing. Conversely, IL-10 can activate STAT3 encouraging migration of epithelial cells to the cornea. IL-10 can also suppress cytokine production, inhibiting inflammation. C. mast is an eye-colonizing bacterium that has been genetically manipulated using transposon mutagenesis to produce and secrete IL-10. This engineered C. mast can continuously deliver IL-10 directly to the wound site to promote healing. This novel therapy would not require multiple daily applications, unlike eyedrops which many patients find uncomfortable, reducing compliance, and would not be diluted or washed away by tears.
Invention Readiness
C. mast was genetically engineered to produce and secrete mouse IL-10 (IL-10-C. mast). Animals were ocularly inoculated with 1x10⁶ CFU of IL-10-C. mast a total of three times over five days. Corneas were wounded two weeks later. The rate of wound healing in animals inoculated with IL-10-C. mast, was significantly increased compared to control animals. C. mast has now been engineered to secrete human IL-10, the first ocular bacterium engineered to secrete a human cytokine. Future work could identify a variety of bacteria that could be engineered to secrete other therapeutics, providing a novel method to deliver therapeutic agents to mucosal surface sites such as the mouth, nose, lungs, and gastrointestinal tract.
IP Status
Patent Pending
Related Publication(s)
Xu, X., Rigas, Y. E., Mattapallil, M. J., Guo, J., Nagarajan, V., Bohrnsen, E., Richards, C., Gupta, A., Gaud, G., Love, P. E., Jiang, T., Zhang, A., Xu, B., Peng, Z., Jittayasothorn, Y., Carr, M., Magone, M. T., Brandes, N. T., Shane, J., … Caspi, R. R. (2025). Commensal-derived Trehalose Monocorynomycolate Triggers γδ T Cell-driven Protective Ocular Barrier Immunity. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2025.03.17.643820
Leger, A. St., Shane, J., Evans, M., Rigas, Y., & Shanks, R. (2024). The Generation of an ocular anti-inflammatory biotherapeutic to enhance wound healing. Springer Science and Business Media LLC. https://doi.org/10.21203/rs.3.rs-4354377/v1
