One of the most vital tools of genetics is the CRISPR/Cas9 system. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. This system is used to edit genetics by using the transfection of a plasmid in target cells. Within the plasmid, there are four components that include: crRNA, trancRNA, sgRNA, and Cas9. crRNA is the guide RNA used for locating the DNA along the strain that is in particular interest of editing. TranscRNA works with crRNA to form an active complex for the editing process to take places. SgRNA also acts as guide for both of the components previously discussed. Cas9 is the part that is able to modify the DNA (1). In order to incorporate these components, a virus is used, often an adeno-virus. Although this system sounds complex, many are using it as the hope of the future to cure genetic diseases with one in particular focus being on Multiple Dystrophy (MD).
MD is a disease of the central nervous system that is inherited through a X-linked recessive pattern, making it more prominent among men than women, that often results in premature death (2, 3). The central nervous system consists of the brain, spinal cord, and optic nerves. When MD occurs, a person’s immune response mistakenly attacks the nervous system causing the deteoriation of the myelin, which is the conductor surrounding the nerves, due to inflammation (2). In order to understand this complex process, model organisms have been used, such as dogs.
Researchers identified beagle puppies that had a genetic mutation resembling the effects of MD in humans which causes muscle weakness and degeneration over time (3). By using the CRISPR/Cas9 system, researchers were able to repair the mutation in exon 51, which relieved the symptoms in the dogs (4). For dogs, the specific mutation was for making a protein called dystrophin, which is responsible for muscle structure and function. After using the CRISPR/Cas9 system, the researchers looked into the dystrophin levels over a period of time and found that in eight weeks the muscles began to show an increase in the protein levels. A previous study has found that an increase of dystrophin levels by 15% could help to alleviate the symptoms of those with MD (3). Looking specifically at the heart muscles of the beagles, researchers found 92% restoration of heart muscles’ dystrophin levels (5). This news is something to note as it will pave the way for editing genomes with the potential of one day being able to help patients with genetic diseases.
- Barrangou, R. (2015). The roles of CRISPR–Cas systems in adaptive immunity and beyond. Current Opinion in Immunology, 32, 36–41. https://doi.org/https://doi.org/10.1016/j.coi.2014.12.00
- “About Neuromuscular Diseases.” Muscular Dystrophy Association, 31 Aug. 2018, http://www.mda.org/disease.
- L. Amoasii et al. Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy. Science. Published online August 30, 2018. doi:10.1126/aau1549.
- Daley, Jason. “Gene Editing Treats Muscular Dystrophy in Dogs.” Smithsonian.com, Smithsonian Institution, 31 Aug. 2018, www.smithsonianmag.com/smart-news/gene-editing-treats-muscular-dystrophy-dogs-180970184/.
- UT Southwestern Medical Center. “CRISPR halts Duchenne muscular dystrophy progression in dogs.” ScienceDaily. ScienceDaily, 30 August 2018. <www.sciencedaily.com/releases/2018/08/180830143205.htm>.