Phosphorodiamidate morpholino oligonucleotides (morpholinos) are non-classical antisense reagents that modulate gene expression by inhibiting protein translation or inducing alternative splicing events. They are synthetic molecules that are the product of a redesign of natural nucleic acid structure. Usually 25 bases in length, they bind to complementary sequences of RNA by standard nucleic acid base-pairing. In terms of structure, the difference between Morpholinos and DNA is that, while Morpholinos have standard nucleic acid bases, those bases are bound to morpholine rings instead of deoxyribose rings and linked through phosphorodiamidate groups instead of phosphates.
Morpholinos do not degrade their target RNA molecules, unlike many antisense structural types (e.g., phosphorothioates, siRNA). Instead, Morpholinos act by "steric blocking", binding to a target sequence within an RNA and simply getting in the way of molecules that might otherwise interact with the RNA. In detail, The effect morpholinos cause on the expression is determined by the position targeted within a nucleotide sequence. Morpholinos targeting the 5′-untranslated regions (5′-UTRs) in proximity to the translational initiation site (TIS) disrupt ribosomal complex formation and inhibit protein translation of mRNA, while morpholinos targeting pre-mRNA splice sites can induce alternative splicing events.