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Gene therapy approaches to the Duchenne muscular dystrophy treatment

Genes & Cells: Vol XIV, №4, 2019, pp: 6-18 DOI: 10.23868/201912026


M.I. Zaynitdinova, S.A. Smirnikhina, A.V. Lavrov, I.I. Eremin, A.A. Pulin

Duchenne muscular dystrophy (DMD) is a common genetic disease which develops as a result of a mutation in the gene encoding dystrophin. In this review, the main experimental therapeutic approaches based on gene therapy are described. Independence of the type of mutation in the DMD gene is an advantage of the viral delivery of micro- and minidystrophin in muscle cells, but this method provides only a temporary effect. The specificity of the mutation also does not matter with an increase in the level of utrophin, however, this protein cannot fully replace dystrophin. The drugs which promote reading through the stop codon have low efficiency and are suitable for only 10–15% of patients with DMD. The most promising approach for the treatment of DMD is the exon skipping, which will suit 90% of patients. It can be implemented by antisense oligonucleotides or using the CRISPR/Cas9 genome editing system. CRISPR/Cas9-mediated exon skipping is thought to be the most promising approach, because it allows to make the necessary changes in the genome with great efficiency after single application.

Keywords: Duchenne muscular dystrophy, dystrophin, gene therapy, exon skipping, antisense oligonucleotide, CRISPR/Cas9.

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