Phosphorodiamidate morpholino oligonucleotides (PMOs) of 20-30 nucleotides long have demonstrated exceptional properties compared to other antisense oligonucleotides as gene silencing reagents. These include high sequence specificity, water solubility, sufficient endonuclease stability and minimal off-target effects (non-antisense effects). PMOs function through a steric blocking mechanism, binding to a target mRNA sequence to prevent translation and also used as a splice correction reagents during pre-mRNA splicing.

A Morpholino oligo is radically different from natural nucleic acids, with methylenemorpholine rings replacing the ribose or deoxyribose sugar moieties and non-ionic phosphorodiamidate linkages replacing the anionic phosphates of DNA and RNA. Each morpholine ring suitably positions one of the standard DNA bases (A,C,G,T) for pairing, so that a Morpholino oligo strongly and specifically binds to its complementary target site in a strand of RNA via Watson-Crick pairing. Because the uncharged backbone of the Morpholino oligo is not recognized by enzymes, it is completely stable to nucleases.