OptiDicer reduces long CUG RNA accumulation in corneal endothelial cells from patients with Fuchs' dystrophy
| dc.contributor.advisor | Ambati, Balamurali | |
| dc.contributor.author | Basak, Sanjana | |
| dc.date.accessioned | 2024-08-30T19:08:50Z | |
| dc.date.available | 2024-08-30T19:08:50Z | |
| dc.date.issued | 2024 | |
| dc.description | 30 pages | |
| dc.description.abstract | This study will examine the viability of the modified endonuclease, known as OptiDicer, in preventing corneal endothelial cell loss and halting the progression of late-onset Fuchs’ Endothelial Corneal dystrophy (FECD). FECD is a debilitating, heritable disease that could impact 415 million people by the year 2050 (Aiello et al., 2022). The consequences of this disease are significant and include loss of vision, painful corneal edema, and collagen excrescences. The current treatment for FECD involves surgical transplantation of donor corneas. This treatment is limited in its capability due to high costs, high transplant rejection and infection rates, and painful long recuperation periods. Developing a targeted gene therapy such as OptiDicer could provide a watershed medical care advancement for patients suffering from late-onset FECD. This disease manifests from a progressive decrease in corneal endothelial cell density. Prior research indicates that a trinucleotide expanded repeat mutation in the TCF4 gene affects diseased corneal endothelial cells. The excessive repetition of the CTG nucleotide in this gene leads to the overproduction of CUG RNA in the cell nucleus. The overabundance of RNA forms distinct structures, or foci, which are toxic to the corneal endothelial cells. Our treatment, 3 OptiDicer, is a modified form of the endogenous protein DICER1 that cleaves CUG RNA in cell nuclei via RNase III activity. Unlike DICER1, OptiDicer is miRNA-resistant and can continuously cleave accumulated CUG RNA foci. We expect that OptiDicer will significantly reduce CUG RNA foci in corneal endothelial cell nuclei and prevent endothelial cell death in the cornea. | en_US |
| dc.identifier.orcid | 0009-0008-9848-4918 | |
| dc.identifier.uri | https://hdl.handle.net/1794/29882 | |
| dc.language.iso | en_US | |
| dc.publisher | University of Oregon | |
| dc.rights | CC BY-NC-ND 4.0 | |
| dc.subject | Molecular Biology | en_US |
| dc.subject | Gene Therapy | en_US |
| dc.subject | Heritable Disease | en_US |
| dc.subject | Fuchs' dystrophy | en_US |
| dc.subject | Cornea | en_US |
| dc.title | OptiDicer reduces long CUG RNA accumulation in corneal endothelial cells from patients with Fuchs' dystrophy | |
| dc.type | Thesis/Dissertation |