antisense oligonucleotide (phosphoromorpholino oligomer)

The drug is a splice-modulating antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) chemistry, designed to target a recurrent deep intronic mutation in the COL6A1 gene (c.930+189C>T). This mutation creates a cryptic splice donor site, leading to the insertion of an in-frame pseudoexon in the mature COL6A1 mRNA, which encodes a mutant collagen α1(VI) chain that exerts a dominant-negative effect on collagen VI matrix assembly. By binding to the pre-mRNA (specifically targeting pseudoexon internal sites or splice junctions, with PMO-PEX1 being a lead sequence), the PMO blocks the splicing machinery, effectively skipping the pseudoexon and restoring the production of wild-type collagen VI. This therapeutic approach is being developed by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) for the treatment of collagen VI-related muscular dystrophies (COL6-RD), including Ullrich congenital muscular dystrophy (UCMD) and Bethlem muscular dystrophy.

Other names

COL6A1-targeting PMOCOL-6A1-targeting PMOCOL 6A1-targeting PMOCOL6A1-targeting antisense oligonucleotideCOL-6A1-targeting antisense oligonucleotideCOL 6A1-targeting antisense oligonucleotidephosphoromorpholino oligomer