DNA at the intronic IVS50 5' splice site of the human DMD gene (DMD IVS50 5'SS)

The target is a specific genomic DNA sequence located at the 5' splice site (donor site) of intron 50 in the human DMD gene. This site is critical for the correct recognition and splicing of exon 50 into the mature dystrophin mRNA. In therapeutic development for Duchenne Muscular Dystrophy (DMD), this DNA sequence is targeted by base-editing technologies to modify the splice signal and induce the skipping of exon 50. By bypassing exon 50 during splicing, the reading frame of the DMD gene can be restored in patients with specific out-of-frame deletions, such as those lacking exon 51 or exons 51-53. This approach, exemplified by the experimental drug GEN6050, aims to produce a truncated but functional dystrophin protein. Unlike antisense oligonucleotides that target RNA and require chronic administration, DNA-level editing at this site offers the potential for a permanent, one-time therapeutic correction.

Other names

Dystrophin gene intron 50 5' splice siteDMD intron 50 donor splice siteDMD IVS50 5'SSDystrophin IVS50 5'SSDMD exon 50-intron 50 junction

Base editing of the DNA at the 5' splice site of intron 50 to disrupt the donor splice signal and induce exon 50 skipping