Precision therapeutics for genetic disorders with transfer ribonucleic acids

Transfer ribonucleic acid (tRNA) therapeutics will provide personalized and mutation specific medicines to treat human genetic diseases for which no cures currently exist. The tRNAs are a family of adaptor molecules that interpret the nucleic acid sequences in our genes into the amino acid sequences of proteins that dictate cell function. Humans encode more than 600 tRNA genes. Interestingly, even healthy individuals contain some mutant tRNAs that make mistakes. These include missense suppressor tRNAs that insert the wrong amino acid in proteins, and nonsense suppressor tRNAs that read through premature stop signals and generate full length proteins. Mutations that underlie more than 50% of inherited genetic diseases, including neurodegeneration, cancers, and rare genetic disorders result from missense or nonsense mutations. Thus, specific tRNA variants can be strategically deployed as therapeutic agents to correct genetic defects. We will develop novel tRNA therapeutics to correct nonsense mutations that cause amyotrophic lateral sclerosis and Duchenne muscular dystrophy. We will also investigate missense suppressor tRNAs that reduce the production and aggregation of the defective protein that causes Huntington's disease. By allowing a functional protein to be produced from a disease-causing gene, tRNA therapeutics will provide a new direction to ameliorate or cure genetic defects that cause neurodegeneration and muscular dystrophy.