Jackie Bower, PhD (UNC-CH)
Matt Hirsch, PhD (UNC-CH)
Brian Gilger, DVM (NCSU)
A cross-disciplinary UNC-North Carolina State University (NCSU) team with collaborative ties in developing ocular drug delivery systems has recently discovered a genetically engineered pathway to reduce corneal blindness via decreasing rejection of high-risk corneal transplantation (CT). In the November 6th, 2024 Molecular Therapy, two UNC Ophthalmology basic scientists — Research Assistant Professor Jackie Bower, PhD, and lead study author Associate Professor Matt Hirsch, PhD — collaborated with NCSU Professor of Ophthalmology Brian Gilger, PhD — in publishing a study entitled, “A chimeric anti-vascularization immunomodulator prevents high-risk corneal transplantation rejection via ex vivo gene therapy.”
In this study, adeno-associated virus (AAV) ex vivo gene therapy was employed to establish immune tolerance in the corneal allograft to prevent high-risk CT rejection. Building on prior research that demonstrated human leukocyte antigen G (HLA-G)-boosted ocular immune privilege, the research team engineered a single-chain immunomodulator (scIM) mimicking the structural conformation and function of the potent HLA-G homodimer complex. In this Molecular Therapy study, AAV-scIM was injected to the subconjunctival space to reduce trauma induced corneal vascularization and fibrosis in a murine model. Then, ex vivo AAV-scIM gene delivery to corneal allografts reduced high-risk CT rejection in a leporine model.
Study data collectively demonstrate that scIM gene therapy prevents corneal neovascularization, reduces trauma-induced corneal fibrosis, and prevents allogeneic CT rejection in a high-risk large animal model. The results also promote further study and discovery of therapeutic tissue engineering mechanisms for treating corneal blindness, a disease that affects more than five million individuals worldwide. This work was supported by the NIH and Bedrock Therapeutics, Inc. a UNC spinout biotech company co-founded by Drs. Gilger and Hirsch that is advancing these promising results towards a Phase I clinical trial.
Dr. Hirsch, an AAV-gene delivery engineering expert, added, “While the work herein demonstrates Proof-of-Concept for ex vivo scIM gene therapy to prevent corneal transplant rejection, our optimism is growing towards broader applications to prevent immunological rejection of other organs including the heart, liver, and kidneys.”
To read more on this UNC-NCSU collaborative study, refer to the November 6, 2024 issue of Molecular Therapy.