The administration of a nucleoside-modified messenger RNA sequence can cause a cell to make a protein, which in turn could directly treat a disease or could function as a vaccine; more indirectly the protein could drive an endogenous stem cell to differentiate in a desired way.
The primary challenges of RNA therapy center on delivering the RNA to the appropriate cells. Challenges include the fact that naked RNA sequences naturally degrade after preparation; they may trigger the bodys immune system to attack them as an invader; and they are impermeable to the cell membrane. Once within the cell, they must then leave the cells transport mechanism to take action within the cytoplasm, which houses the necessary ribosomes.
Overcoming these challenges, mRNA as a therapeutic was first put forward in 1989 "after the development of a broadly applicable in vitro transfection technique." In the 1990s, mRNA vaccines for personalized cancer have been developed, relying on non-nucleoside modified mRNA. mRNA based therapies continue to be investigated as a method of treatment or therapy for both cancer as well as auto-immune, metabolic, and respiratory inflammatory diseases. Gene editing therapies such as CRISPR may also benefit from using mRNA to induce cells to make the desired Cas protein.
Since the 2010s, RNA vaccines and other RNA therapeutics have been considered to be "a new class of drugs". The first mRNA-based vaccines received restricted authorization and were rolled out across the world during the COVID-19 pandemic by Pfizer–BioNTech COVID-19 vaccine and Moderna, for example.
The 2023 Nobel Prize in Physiology or Medicine was awarded to Katalin Karikó and Drew Weissman for the development of effective mRNA vaccines against COVID-19.