What is "morpholino"

n. (context genetics English) A structural analog of natural nucleic acid used to modify gene expression, in which the ribose or deoxyribose rings of nucleic acids are replaced with morpholine rings and the phosphodiester intersubunit linkages of nucleic acids are replaced with phosphorodiamidate linkages. See the Wikipedia page on "Morpholino" for a drawing of a representative Morpholino structure.

A morpholino, also known as a morpholino oligomer and as a phosphorodiamidate morpholino oligomer (PMO), is type of oligomer molecule (colloquially, an oligo) used in molecular biology to modify gene expression. The molecular structure has a backbone of methylenemorpholine rings and phosphorodiamidate linkages. Morpholinos block access of other molecules to small (~25 base) specific sequences of the base-pairing surfaces of ribonucleic acid (RNA). Morpholinos are used as research tools for reverse genetics by knocking down gene function. They are being studied for application in medicine.

This article discusses only the morpholino antisense oligomers, which are nucleic acid analogs. The word "morpholino" can occur in other chemical names, referring to chemicals containing a six-membered morpholine ring. To help avoid confusion with other morpholine-containing molecules, when describing oligos "Morpholino" is often capitalized as a trade name, but this usage is not consistent throughout the scientific literature.

Gene knockdown is achieved by preventing cells from making a targeted protein. Morpholinos can also modify the splicing of pre-mRNA. Knocking down gene expression is a powerful method for learning about the function of a particular protein; in a similar manner, causing a specific exon to be spliced out of a protein can help to determine the function of the protein moiety encoded by that exon or can sometimes knock down the protein activity altogether. These molecules have been applied to studies in several model organisms, including mice, zebrafish, frogs, and sea urchins.

Morpholinos are in development as pharmaceutical therapeutics targeted against pathogenic organisms such as bacteria or viruses and for amelioration of genetic diseases. These synthetic oligos were conceived by James E. Summerton ( Gene Tools) and originally developed in collaboration with Dwight D. Weller at a biotech corporation (formerly Antivirals, renamed AVI BioPharma, renamed Sarepta Therapeutics). The experimental Morpholino drug eteplirsen from Sarepta Therapeutics is currently (April 2016) in Phase III clinical trials for treatment of some mutations causing Duchenne muscular dystrophy.