Emami, Michael
Michael is in the Cellular and Developmental Biology home area of the MBIDP. He received a B.S. degree from the University of California, Irvine, in 2016, and then came to UCLA and joined the laboratory of Dr. Melissa Spencer. He entered the CMB Training Program in 2017.
Mentor: Dr. Melissa Spencer
Duchenne Muscular Dystrophy (DMD) is an incurable and devastating X-linked genetic disease that is characterized by progressive muscle degeneration. DMD is caused by mutations in dystrophin (DMD gene) that disrupt the reading frame resulting in a loss of functional protein. Dystrophin is a critical member of the dystroglycan complex (DGC) that serves to stabilize the sarcolemmal membrane. However, in the absence of functional dystrophin there is a loss of DGC components, muscle stem cell dysfunction and susceptibility to necrosis. As a consequence, DMD patients experience progressive muscle weakness, are wheelchair-bound in their teens and need a respirator to facilitate breathing. There is currently one FDA approved drug, eteplirsen or exondys 51, which targets 13% of DMD patients by skipping the mutant exon 51 to restore the DMD reading frame. Yet, eteplirsen must be administered once a week because it acts at the mRNA level. Exondys 51 enhances the quality of life for those patients with mutations amenable to skipping exon 51, but the majority of DMD patients are not able to benefit from the drug, due to the nature of their mutations.
Since DMD is a monogenic disease, gene editing strategies such as clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated nuclease (Cas) 9 (CRISPR/Cas9) can be used to engineer site-specific editing and offer a promising and attractive approach for therapy. We have shown previously, that deleting exons 45-55 (~700kb) restores the DMD reading frame. Likewise, we are also interested in developing a strategy that can completely restore the gene using a cDNA donor. We aim to achieve this by using a novel-nanoparticle mediated delivery system. Currently, I am conducting nanoparticle trafficking studies.
