Morpholino oligos are molecules used to bind to RNA and, by getting into the way of macromolecules, to modify cellular processes. Morpholinos can block translation of a targeted mRNA, block splicing of a targeted pre-mRNA or block maturation and activity of a pri-miRNA.

Morpholinos are superficially similar to nucleic acids, but while they have DNA bases linked to their backbones, the backbones themselves are non-natural. The backbone of a Morpholino oligo has morpholine rings instead of ribose (or deoxyribose) and has uncharged phosphorodiamidate linkages instead of anionic phosphodiesters. Morphlinos are typically synthesized bearing 18 to 31 nucleic acid bases.

A Morpholino is uncharged and does not interact strongly with proteins. A Morpholino is not cleaved by nucleases or other lytic enzymes, it does not interact with Toll-like receptors and hence does not stimulate innate immune responses, and it does not require enzymes such as RNase-H or Argonaute for its activity so it is more specific than phosphorothioate antisense or siRNAs.

Morpholinos are commonly used in developmental biology. The embryo is an exquisitely sensitive system to toxins or off-target gene modulation. Morpholinos have sufficient specificity and non-toxicity to perform effectively in embryonic knockdown experiments. The stability of a Morpholino in vivo allows many experiments starting with oocyte injection to last for 5 to 7 days into development.

Morpholinos are also effective in cell cultures and in some in-vivo applications in adult organisms. Delivery of the oligos into the cytosol of cells is a challenge for many in-vivo applications. New technologies, such as covalently-linked cell penetrating peptides, are making Morpholinos more effective for in vivo applications.