Messenger RNA Silencing of UBASH3A in Type 1 Diabetes
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Author/Creator
Author/Creator ORCID
Date
2021-04-26
Type of Work
Department
Hood College Biology
Program
Biomedical science (M.S.)
Citation of Original Publication
Rights
CC0 1.0 Universal
Abstract
This project is aimed to investigate micro-RNA as a potential therapeutic approach for silencing
ubiquitin-associated and SH3-domain-containing A (UBASH3A), a negative regulator of the NF-kB pathway
in CD4+ T cell Receptor and CD-28 signaling. UBASH3A expression is upregulated in patients of Type-1
Diabetes (T1D) who harbor risk alleles RS11203203 and RS80054410 on chromosome 21 resulting in single
nucleotide polymorphisms. Increases in UBASH3A decrease IL-2 and therefore T1Ds experience pathogenesis
via lack of T regulatory (T reg/T-reg) cell development from the loss of the pleiotropic cytokine. It has
previously been shown, using clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated
protein 9 (Cas-9) edited CD4+ T cells, that the silencing of UBASH3A results in a decrease in the
protein and an increase of IL-2 production. This study will determine if the use of micro-RNA directed
towards the UBASH3A messenger RNA can reduce UBASH3A protein and rescue IL-2 production in T cells.
This work will pave the way for future studies that aim to treat patients with T1D.