Phosphorodiamidate morpholino oligomer (PMO)

A phosphorodiamidate morpholino oligomer (PMO), commonly known as a Morpholino, is a synthetic antisense molecule used to regulate gene expression by binding to complementary RNA sequences (Summerton & Weller, 1997, Antisense Nucleic Acid Drug Dev). Unlike natural nucleic acids, Morpholinos possess a backbone of morpholine rings connected by phosphorodiamidate linkages, which confers high stability and resistance to enzymatic degradation by nucleases (Moulton & Moulton, 2010, Methods Mol Biol). They operate through a steric blocking mechanism, binding to specific sequences on target mRNA or pre-mRNA to physically prevent the assembly of the translation initiation complex or to redirect the splicing machinery (Heasman, 2002, Dev Biol). This makes them highly effective for applications such as gene knockdown, exon skipping, and the study of gene function in developmental biology (Morcos, 2007, Methods Cell Biol). Clinically, Morpholinos have gained prominence as a therapeutic class for treating Duchenne muscular dystrophy by restoring the reading frame of the dystrophin gene, with several agents currently approved by regulatory bodies (FDA, 2016, Exondys 51 Label).

Other names

MorpholinoMorpholino oligonucleotideAntisense morpholinoMorpholino phosphorodiamidate oligomer

Steric blocking of target RNA sequences to prevent translation or modify pre-mRNA splicing.