由于剪接缺陷、插入、缺失或点突变（也称为无义突变）而引入过早终止密码子 (PTC)，会导致多种遗传疾病，从罕见的神经代谢紊乱到相对常见的遗传性癌症综合征和肌肉营养不良症。多年来，大量研究表明，某些抗生素和其他合成分子可以通过诱导无义突变的通读来充当 PTC 抑制剂，从而恢复全长蛋白质的表达。不幸的是，大多数 PTC 通读诱导剂都是有毒的，作用有限，并且不能用于治疗目的。因此，需要进一步努力来改善无义突变抑制因子的临床结果。在这里，通过重点加强对腺瘤性息肉病大肠杆菌 (APC) 肿瘤抑制基因中致病性无义突变的通读，我们发现，干扰蛋白质翻译起始复合物以及针对蛋白质翻译机制的其他阶段，可以增强抗生素和非抗生素治疗的效果。 -抗生素介导的无义突变的通读。这些发现极大地增进了我们对无义突变通读所涉及机制的理解，并促进了无义抑制的新治疗靶点的开发，以恢复多种致病突变转录本的蛋白质表达。版权所有：© 2023 Wittenstein 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

The introduction of premature termination codons (PTCs), as a result of splicing defects, insertions, deletions, or point mutations (also termed nonsense mutations), lead to numerous genetic diseases, ranging from rare neuro-metabolic disorders to relatively common inheritable cancer syndromes and muscular dystrophies. Over the years, a large number of studies have demonstrated that certain antibiotics and other synthetic molecules can act as PTC suppressors by inducing readthrough of nonsense mutations, thereby restoring the expression of full-length proteins. Unfortunately, most PTC readthrough-inducing agents are toxic, have limited effects, and cannot be used for therapeutic purposes. Thus, further efforts are required to improve the clinical outcome of nonsense mutation suppressors. Here, by focusing on enhancing readthrough of pathogenic nonsense mutations in the adenomatous polyposis coli (APC) tumor suppressor gene, we show that disturbing the protein translation initiation complex, as well as targeting other stages of the protein translation machinery, enhances both antibiotic and non-antibiotic-mediated readthrough of nonsense mutations. These findings strongly increase our understanding of the mechanisms involved in nonsense mutation readthrough and facilitate the development of novel therapeutic targets for nonsense suppression to restore protein expression from a large variety of disease-causing mutated transcripts.Copyright: © 2023 Wittenstein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.