Date of Graduation

5-2020

Document Type

Thesis

Degree Name

Bachelor of Science in Biomedical Engineering

Degree Level

Undergraduate

Department

Biomedical Engineering

Advisor/Mentor

Nelson, Christopher

Committee Member/Reader

Rao, Raj

Committee Member/Second Reader

Quinn, Kyle

Committee Member/Third Reader

Jensen, Hanna

Abstract

Duchenne muscular dystrophy (DMD) affects approximately 1 in 5,000 males. DMD results from genetic mutations within the gene that interrupts the open reading frame and prematurely truncates the protein. From a non-functional dystrophin protein, DMD results in serious muscle weakening and muscle wasting ultimately leading to death around the age of 26. In some cases of muscular dystrophy, a mutation can occur in areas of the gene that are less essential. In Becker muscular dystrophy (BMD), these mutations cause less significant consequences in phenotype as the dystrophin protein is still semi-functional. With gene editing techniques, it may be possible to reduce the consequences of the DMD phenotype. Exon skipping is a process that advertently skips specific and surrounding exons that have been harmfully mutated. This process could potentially be used to skip specific exons in the DMD gene necessary to bring the RNA transcript back into the correct reading frame. This study focuses on the theoretical application of exon skipping in DMD. Using data of all the recorded mutations up to now, the study looks at the separate effects skipping each exon has on the three different types of mutations: deletions, duplications, and small rearrangements. Exon skipping was modeled computationally. Under an important operational assumption, the results were encouraging. Theoretically, skipping the top eight most effective exons would correctly reframe just above 50% of the total mutations. Skipping exon 51 alone would restore the reading frame in 14% of patients. This study focused primarily on the results of skipping only one exon at a time. While there is still much more work to do to find the true applicability of exon skipping in DMD, the results provide a solid framework and guide to what comes next.

Keywords

Exon skipping, gene editing, CRISPR, Duchenne Muscular Dystrophy

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