Transfer RNAs (tRNAs) were originally conceptualized through the adaptor hypothesis as essential yet functionally inert intermediates in translating the genetic information into protein. More recently, tRNAs have emerged as dynamic regulators of protein biogenesis and, increasingly, as potential therapeutic agents. In this talk, Prof. Ignatova will present their recent advances in the development of tRNA-based therapeutics with high activity and favorable safety profiles in both cellular and animal models.
tRNA therapeutics offer a promising approach to addressing nonsense mutation–associated genetic disorders, which constitute the largest class of genetic diseases and account for approximately 11% of all cases. Nonsense mutations introduce premature termination codons (PTCs) into protein-coding sequences, leading to early translational termination and loss-of-function phenotypes. To overcome this challenge, we leverage advances in tRNA biology and function to repurpose natural sense-codon-decoding tRNAs to promote selective readthrough of PTCs. This approach restores full-length protein synthesis and rescues functional activity, highlighting the therapeutic potential of engineered tRNAs for previously inaccessible genetic targets.