mRNA therapy (NORD)

DNA is the genetic code bound within chromosomes inside the nucleus, or the center, of each cell. It contains directions for making proteins, which is done in ribosomes outside the nucleus. But, DNA can’t leave the nucleus, so it produces a copy of itself, called messenger RNA or mRNA, which can carry the blueprint for making proteins outside the nucleus. Proteins are key to the structure and function of each cell, such as supporting the cell’s outer barrier or membrane, executing chemical reactions, and clearing harmful substances.  

Genetic disorders occur when there are one or more changes in the sequence of specific units of DNA known as genes. These changes may disrupt the production of functional protein, leading to health problems. For example, there may be a breakdown in regulating what goes into and out of cells because important membrane structures aren’t working, or toxic substances may build up within cells because there aren’t enough functioning proteins to break them down efficiently.  

mRNA therapy is being studied to treat many different health conditions, including some rare genetic disorders caused by protein deficiencies. Researchers believe mRNA therapy can provide the blueprints that cells need to make properly functioning protein, thereby reducing symptoms, modifying the course of disease, and improving quality of life. This approach uses mRNA as a protein replacement therapy.    

As a protein replacement therapy, the specific mRNA unit needed to make the missing or dysfunctional protein is administered. Therapeutic mRNA is usually transported to cells by lipid nanoparticles, which are tiny fat bubbles that surround and protect mRNA. It may be given as an infusion into the bloodstream. mRNA therapy needs to be given at regular intervals because the therapeutic mRNA is broken down in the body.  

mRNA therapy is being developed for several conditions including lysosomal storage disorders; cystic fibrosis, or CF; and familial hypercholesterolemia, or FH. 

Lysosomal storage disorders are a group of genetic conditions that are a result of problems in the structure or function of the lysosome, or the cell’s waste processing center.  Most lysosomal storage disorders are caused by genetic changes that result in reduced production of one of multiple lysosomal enzymes. Lysosomal enzymes help cells get rid of waste products. In Gaucher disease, for example, the enzyme glucocerebrosidase does not work well, and fatty material that typically is broken down by this enzyme builds up in the liver, spleen and bone marrow. mRNA therapy for Gaucher disease aims to provide the blueprint to manufacture glucocerebrosidase so the cells can once again get rid of excess waste products and reduce symptoms of the disease.