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. Missense suppressor tRNAs insert the wrong amino acid in proteins, and nonsense suppressor tRNAs read through premature stop signals to generate full length proteins. Mutations that underlie many human diseases, including neurodegenerative diseases, cancers, and diverse 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 review the mechanisms of tRNA therapeutic activity, the nature of the therapeutic window for nonsense and missense suppression as well as wild-type tRNA supplementation. We discuss the challenges and promises of delivering tRNAs as synthetic RNAs or as gene therapies. Together, tRNA medicines will provide novel treatments for common and rare genetic diseases in humans.

中文翻译：

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tRNA 治疗的机制和递送


转移核糖核酸（tRNA）疗法将提供个性化和突变特异性药物来治疗目前尚无治愈方法的人类遗传疾病。 tRNA 是一个接头分子家族，它将我们基因中的核酸序列解释为决定细胞功能的蛋白质的氨基酸序列。人类编码 600 多个 tRNA 基因。有趣的是，即使是健康的个体也含有一些会出错的突变 tRNA。错义抑制 tRNA 在蛋白质中插入错误的氨基酸，无义抑制 tRNA 读取过早停止信号以生成全长蛋白质。许多人类疾病的突变，包括神经退行性疾病、癌症和各种罕见的遗传性疾病，都是由错义或无义突变引起的。因此，特定的 tRNA 变体可以战略性地用作治疗剂来纠正遗传缺陷。我们回顾了 tRNA 治疗活性的机制、无义和错义抑制的治疗窗口的性质以及野生型 tRNA 补充。我们讨论了将 tRNA 作为合成 RNA 或基因疗法提供的挑战和前景。 tRNA 药物将为人类常见和罕见遗传疾病提供新的治疗方法。