3rd Place


Alvin Ya

Poolesville High School 
Teacher: Mary Alice Adah


Muscular dystrophies are a group of heterogenous genetic disorders characterized by the wasting of skeletal muscle mass resulting in progressive weakness (NINDS, n.d.). Of the over thirty diseases identified to be muscular dystrophies, Duchenne muscular dystrophy (DMD, MIM 310200) is the most prevalent, affecting an estimated 1 in 3600 males globally (Chung et al., 2015). Obvious symptoms are not present at birth but progress quickly. Patients often exhibit decreased muscle mass and trouble walking at about 3-5 years of age (Pane et al. 2013), and beyond the age of 10 years the development of weakness and scoliosis aligns with the necessity for a wheelchair (Mazzone et al., 2011). Life expectancy has traditionally been between 20-30 years due to the development dilated cardiomyopathy leading to respiratory and cardiac complications (Van Westering et al., 2015)…

DMD is caused by mutations in the dystrophin gene (MIM 300377) located on the X chromosome between positions Xp21.2 – Xp21.1 (Hoffman et al., 1987; Genetics Home Reference, 2017). Mutations in the dystrophin gene are also related to Becker muscular dystrophy (BMD, MIM 300376) characterized by significantly less severe symptoms (Kingman et al., 1984; Genetics Home Reference, 2017). Since the discovery of the gene in 1986 (Monaco et al., 1986), the genetic mechanisms of DMD and BMD have been relatively well understood making it an appealing candidate for gene therapy…

…Studies have shown that conventional gene therapy methods utilizing the adeno-associated viral (AAV) vectors are unable to fully accommodate the large size of the dystrophin gene (Mays et al., 2011), but truncated (mini–) dystrophin has been utilized to treat BMD patients with limited success (Harper et al., 2002; Seto et al., 2014). The primary issue these methods face include low-levels of dystrophin even with restoration and the presence of dystrophin-specific T-cells that may cause immune responses to self and non-self dystrophin (Mendell, 2010)…

…The CRISPR/Cas9 system allows for the precise and versatile editing of genomic information through the usage of guide RNAs (gRNA) to direct the Cas9 nuclease to the desired editing site (Mali et al., 2012)….In vitro studies have shown that CRISPR/Cas9 can succeed in correcting dystrophin mutations in DMD patient stem cells and myoblasts (Ousterout et al., 2015; Li et al., 2015). CRISPR/Cas9 therapies have also found success in the process of in vivo gene editing in dystrophic mdx mice (Xu et al., 2016; Nelson et al., 2016). Despite current success, the technology is still in its infancy and further evaluation will be necessary to truly understand the full ramifications of genome editing with CRISPR/Cas9…