mRNA replacement therapy works
Munich – For the first time, researchers have provided evidence that mRNAs can be used as drugs. By repairing genetic defects in knock-out mice, a team under Carsten Rudoph from Ludwig-Maximilians University in Munich demonstrated that transcript replacement therapy has an effect (Nat Biotechn., doi: 10.1038/nbt.1733).
Before treating mice with a hereditary lung defect, Rudolph replaced roughly a quarter of all uridine and cytidine moieties with 2-thiouridine and 5-methyl-cytidine as mRNA building blocks. “Modification of the mRNA drastically reduced TLR-mediated immunogenicity and at the same time significantly improved mRNA stability,” said Rudoph. Inhalation of an mRNA aerosol, which encoded the surfactant protein B (SF-B), significantly prolonged overall survival of the SF-B-deficient mice. They usually die after 3 days due to a lung defect. SF-B mRNA delivery twice a day over 4 weeks prolonged survival time to 26±2 days. Rudolph and his colleague Christian Plank, who co-founded Seefeld-based Ethris GmbH, now want to commercialise their SNIM® technology. “Our goal is to apply our SNIM® mRNAs locally in regenerative therapies, i.e. as a treatment for diabetes ulcers,” explained Ethris-CEO Rudolph. Other potential applications are local in vivo production of therapeutic proteins or mRNA therapies, which do not show the limitations of DNA-based gene therapies such as activation of oncogenes (cancer) or poor transfection rates. According to Rudolph, the technology is almost ready for market. He said he “hopes to start clinical trials in regmed settings in 2 or 3 years.”