RNA Therapeutics

About

Brief Description A method to suppress premature translation termination and NMD to generate full-length protein using target-specific guide RNAs.     Advantages   A disease-modifying therapy for conditions caused by nonsense mutations, such as Duchenne or Becker muscular dystrophies and cystic fibrosis has long been sought, but to date, none has been found. A few therapies at various clinical phases of development either address the already-mutated RNA, or simply ameliorate the symptoms of the diseases. This invention is aimed to generate functional full length mRNAs and subsequently proteins to provide a cure for the diseases.     Applications   Researchers at the University of Rochester have developed a method for the site-specific conversion of a target uridine within an RNA chain into a pseudouridine through the introduction of a target-specific guide RNA into the cells. Guide RNAs can be conveniently designed and remain stable in vivo throughout the lifetime of the cells. Remarkably, uridine-to-pseudouridine conversion at a pre-mature stop codon of an mRNA results in NMD (nonsense-mediated mRNA decay) suppression and stop codon read-through (aka nonsense suppression), and consequently, synthesis of the full-length protein is restored. This approach can therefore be applied to diseases that are caused by nonsense mutations (e.g., some Duchenne muscular dystrophy patients bearing a nonsense mutation in the dystrophin gene, and some cystic fibrosis patients who have a nonsense mutation in the CFTR gene).