mRNA: Fulfilling the Promise of Gene Therapy

In vitro–transcribed mRNA (IVT mRNA) is emerging as a new class of drug that has the potential to play a role in gene therapy that once was envisioned for DNA.1 Although first described as a therapeutic in 1992,2 IVT mRNA's immunogenicity prevented its development for protein replacement therapies. However, this problem was recently solved by the introduction of modified nucleosides into the IVT mRNA.3 In this issue of Molecular Therapy, Thess and colleagues report an alternative method for generating nonimmunogenic IVT mRNA that avoids the use of modified nucleosides.