ナンセンスバリアントによる遺伝性網膜疾患の治療のためのアンチコドンエンジニアリングtRNA（ACE-tRNA）の潜在的利用

Inherited retinal diseases (IRDs) are clinically and genetically complex disorders that cause blindness in about one in 3450 individuals worldwide. More than 350 genes have been implicated in IRDs showing all possible inheritance patterns. Despite the advancement of several genetic therapies, there is currently no cure for the vast majority of IRDs. By converting a sense codon into a nonsense codon, premature termination codon (PTC) variants cause abrupt termination of protein synthesis, leading to loss of protein function in most cases. Nonsense variants account for approximately 18 % of all disease-causing variants in IRDs, and there is currently no effective treatment available to correct them. In recent years, anticodon engineered tRNAs (ACE-tRNAs) or suppressor tRNAs have emerged as potential therapeutic option for treating rare diseases caused by nonsense variants. This review critically summarizes the spectrum of nonsense variants in the genetics of IRDs and examines the promise of ACE-tRNA therapy as a treatment. We focus on the therapy's mechanism of action, current advancements, and its specific advantages and limitations for addressing nonsense variant-induced IRDs.