Gene Editing With Crispr/Cas9: A New Therapeutic Hope for Duchenne Muscular Dystrophy

In 1861, a French physician, Guillaume Duchenne, first described DMD as “pseudohypertrophic muscle paralysis” that preferentially afflicts males within families”. It is known as one of the most common X-linked diseases, DMD affects 1 in 3500 male newborns and is the result of mutations in the dystrophin gene. Dystrophin is one of the largest known genes in the human genome, containing 79 exons and yielding a 14 kb transcript [1]. Dystrophin protein links the extraand intracellular cytoskeleton, neutralizing stressful events that come from outside the cell to intracellular matrix (Figure 1). When there is a lack of dystrophin protein, there is lack of control for the stress and cell damage occurs [2]. Disease symptoms can vary from mild to severe, depending on the mutation in dystrophin gene. In the case of nonsense mutations, there is a premature stop codon that completely blocks dystrophin translation, resulting in lack of dystrophin and severe clinical presentation. In frame shift mutations, there is an exchange of one nucleotide base with another. Compared to the nonsense mutation, the frame shift mutation of the gene results in a milder clinical presentations. When muscles are biopsied, patients who have milder symptoms typically have less functional or truncated dystrophin. This milder form of disease is often referred to as Becker muscular dystrophy [3].