Duchenne muscular dystrophy is an X-linked recessive hereditary monogenic disorder caused by inability to produce dystrophin protein.In most patients,the expression of dystrophin lost due to disrupting mutations in op...Duchenne muscular dystrophy is an X-linked recessive hereditary monogenic disorder caused by inability to produce dystrophin protein.In most patients,the expression of dystrophin lost due to disrupting mutations in open reading frame.Despite the efforts in a large number of different therapeutic approaches to date,the treatments available for DMD remain mitigative and supportive to improve the symptoms of the disease,rather than to be curative.The advent of CRISPR/Cas9 technology has revolutionized genome editing scope and considered as pioneer in effective genomic engineering.Deletions or excisions of intragenic DNA by CRISPR as well as a similar strategy with exon skipping at the DNA level induced by antisense oligonucleotides,are new and promising approaches in correcting DMD gene,which restore the expression of a truncated but functional dystrophin protein.Also,CRISPR/Cas9 technology can be used to treat DMD by removing duplicated exons,precise correction of causative mutation by HDR-based pathway and inducing the expression of compensatory proteins such as utrophin.In this study,we briefly explained the molecular genetics of DMD and a historical overview of DMD gene therapy.We in particular focused on CRISPR/Cas9-mediated therapeutic approaches that used to treat DMD.展开更多
文摘Duchenne muscular dystrophy is an X-linked recessive hereditary monogenic disorder caused by inability to produce dystrophin protein.In most patients,the expression of dystrophin lost due to disrupting mutations in open reading frame.Despite the efforts in a large number of different therapeutic approaches to date,the treatments available for DMD remain mitigative and supportive to improve the symptoms of the disease,rather than to be curative.The advent of CRISPR/Cas9 technology has revolutionized genome editing scope and considered as pioneer in effective genomic engineering.Deletions or excisions of intragenic DNA by CRISPR as well as a similar strategy with exon skipping at the DNA level induced by antisense oligonucleotides,are new and promising approaches in correcting DMD gene,which restore the expression of a truncated but functional dystrophin protein.Also,CRISPR/Cas9 technology can be used to treat DMD by removing duplicated exons,precise correction of causative mutation by HDR-based pathway and inducing the expression of compensatory proteins such as utrophin.In this study,we briefly explained the molecular genetics of DMD and a historical overview of DMD gene therapy.We in particular focused on CRISPR/Cas9-mediated therapeutic approaches that used to treat DMD.
