Honors Program
Midway Honors
Date of Award
12-2014
Thesis Professor(s)
Zachary Walls
Thesis Professor Department
Pharmaceutical Sciences
Thesis Reader(s)
Ismail Kady, Aruna Kilaru
Abstract
Dystrophia myotonica (DM1), one of the most common forms of muscular dystrophy, is caused by a repeated trinucleotide expansion in the DMPK gene. This mutation results in the accumulation of toxic cellular RNA transcripts. Spliceosome-mediated RNA trans-splicing (SMaRT) technology is a form of gene therapy that possesses the potential to correct these toxic RNA transcripts and thus cure the disease. Despite its promise, prior research applications of SMaRT technology to DM1 have been hampered by poor efficiency and have not been validated in a relevant model of the disease. In order to improve the efficiency of trans-splicing, this study examined the use of novel SMaRT molecules containing altered binding domains. These SMaRT molecules were tested in a clinically relevant cell model of DM1 and their corrective ability compared with that of a standard SMaRT molecule. The results were quantified by RT-PCR. The outcome of this study indicated the need to utilize more specific methods for measuring efficiency and for understanding the specific interactions of SMaRT molecules with target transcripts.
Document Type
Honors Thesis - Open Access
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Recommended Citation
Harrison, Eleanor G., "Redesign of trans-splicing molecules for the correction of dystrophia myotonica type 1 toxic RNA transcripts" (2014). Undergraduate Honors Theses. Paper 248. https://dc.etsu.edu/honors/248
Copyright
Copyright by the authors.