优化 ACE-tRNA 在翻译中的功能，以抑制无义突变。

IF 16.6 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nucleic Acids Research Pub Date : 2024-12-11 DOI:10.1093/nar/gkae1112

Joseph J Porter, Wooree Ko, Emily G Sorensen, John D Lueck

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引用次数: 0

摘要

长期以来，人们一直设想将无义抑制转运核糖核酸（tRNA）或反密码子编辑 tRNA（ACE-tRNA）作为一种治疗方法，以克服因引入过早终止密码子（PTC）而导致的遗传疾病。由于现有的基因治疗方法不能有效地传递ACE-tRNA，因此阻碍了ACE-tRNA挽救PTCs的方法。在这里，我们筛选了一系列 ACE-tRNA 表达盒序列库，其中包含超过 1800 个成员，旨在优化 ACE-tRNA 的功能，并为未来的优化提供路线图。通过优化 ACE-tRNA 对 PTC 的抑制效率，我们将最常见的导致囊性纤维化的 PTC 所需的 ACE-tRNA 量减少了 16 倍。

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Optimization of ACE-tRNAs function in translation for suppression of nonsense mutations.

Nonsense suppressor transfer RNAs (tRNAs) or AntiCodon-Edited tRNAs (ACE-tRNAs) have long been envisioned as a therapeutic approach to overcome genetic diseases resulting from the introduction of premature termination codons (PTCs). The ACE-tRNA approach for the rescue of PTCs has been hampered by ineffective delivery through available modalities for gene therapy. Here we have screened a series of ACE-tRNA expression cassette sequence libraries containing >1800 members in an effort to optimize ACE-tRNA function and provide a roadmap for optimization in the future. By optimizing PTC suppression efficiency of ACE-tRNAs, we have decreased the amount of ACE-tRNA required by ∼16-fold for the most common cystic fibrosis-causing PTCs.

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来源期刊

Nucleic Acids Research 生物-生化与分子生物学

CiteScore

27.10

自引率

4.70%

发文量

1057

审稿时长

2 months

期刊介绍： Nucleic Acids Research (NAR) is a scientific journal that publishes research on various aspects of nucleic acids and proteins involved in nucleic acid metabolism and interactions. It covers areas such as chemistry and synthetic biology, computational biology, gene regulation, chromatin and epigenetics, genome integrity, repair and replication, genomics, molecular biology, nucleic acid enzymes, RNA, and structural biology. The journal also includes a Survey and Summary section for brief reviews. Additionally, each year, the first issue is dedicated to biological databases, and an issue in July focuses on web-based software resources for the biological community. Nucleic Acids Research is indexed by several services including Abstracts on Hygiene and Communicable Diseases, Animal Breeding Abstracts, Agricultural Engineering Abstracts, Agbiotech News and Information, BIOSIS Previews, CAB Abstracts, and EMBASE.