Prime editing allows the introduction of specific mutations in the DMD gene, a new study published in the International Journal of Molecular Sciences reported. 

Based on this finding, the authors of the study concluded that prime editing could therefore be used to correct point mutations in the DMD gene causing Duchenne muscular dystrophy (DMD). 

For the study, the team led by Jacques P. Tremblay, PhD, a professor in the Department of Molecular Medicine at Centre de Recherche du CHUQ-Université Laval, in Québec, Canada, used prime editing to insert specific point mutations in exons 9, 20, 35, 43, 55, and 61 of the DMD gene in HEK293T cells.


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They reported that they obtained up to 11% and 21% of the desired mutations with this approach. When they repeated the treatment 3 times, the percentage of specific mutations increased.

Read more about the symptoms of DMD

The researchers also used the approach to correct the c.428 G>A point mutation in exon 6 of the gene in patient myoblasts. This led to an 8% modification when used once and 28% modification when repeated 3 times. Importantly, the correction led to the expression of dystrophin protein in the myotubes.

Mutations in the DMD gene, which encodes the dystrophin protein, disrupt the reading frame of the gene and cause no functional protein to be made by muscle cells. Around 15% to 30% of all cases of DMD are caused by point mutations while others are caused by large deletions or large duplications in the DMD gene. In the absence of dystrophin, muscle tissue gets damaged at each contraction and is replaced by scar tissue, leading to the symptoms of the disease.

Prime editing is a technique derived from the CRISPR/Cas9 gene-editing technology. It allows the modification of specific nucleotides in a given gene. 

Reference

Mbakam CH, Rousseau J, Tremblay G, Yameogo P, Tremblay JP. Prime editing permits the introduction of specific mutations in the gene responsible for Duchenne muscular dystrophy. Int J Mol Sci. 2022;23(11);6160. doi:10.3390/ijms23116160