TaqTth-hpRNA：特异性沉默致病性 mRNA 的新型紧凑型 RNA 靶向工具。

IF 12.3 1区生物学 Q1 Agricultural and Biological Sciences

Genome Biology Pub Date : 2024-07-07 DOI:10.1186/s13059-024-03326-3

Chong Xu, Jiyanuo Cao, Huanran Qiang, Yu Liu, Jialin Wu, Qiudan Luo, Meng Wan, Yujie Wang, Peiliang Wang, Qian Cheng, Guohua Zhou, Jian Sima, Yongjian Guo, Shu Xu

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引用次数: 0

摘要

致病等位基因沉默是治疗遗传性疾病的一种很有前景的方法。在这里，我们开发了一种 RNA 切割工具 TaqTth-hpRNA，它由小型嵌合 TaqTth 和发夹式 RNA 引导探针组成。体外和体内研究表明，TaqTth-hpRNA 只需要极少的侧翼序列-主题词，就能高效、特异地裂解 RNA。在阿尔茨海默氏症模型中，我们证明了对突变 APPswe mRNA 的沉默，而不改变野生型 APP mRNA。值得注意的是，由于 TaqTth 体积小巧，我们能够在单一 AAV 载体中结合 APOE2 的过表达，从而对病症产生更强的抑制作用。

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TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA.

Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. Here, we develop an RNA-cleaving tool, TaqTth-hpRNA, consisting of a small, chimeric TaqTth, and a hairpin RNA guiding probe. With a minimal flanking sequence-motif requirement, in vitro and in vivo studies show TaqTth-hpRNA cleaves RNA efficiently and specifically. In an Alzheimer's disease model, we demonstrate silencing of mutant APP^swe mRNA without altering the wild-type APP mRNA. Notably, due to the compact size of TaqTth, we are able to combine with APOE2 overexpression in a single AAV vector, which results in stronger inhibition of pathologies.

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来源期刊

Genome Biology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-GENETICS & HEREDITY

CiteScore

25.50

自引率

3.30%

发文量

审稿时长

14 weeks

期刊介绍： Genome Biology is a leading research journal that focuses on the study of biology and biomedicine from a genomic and post-genomic standpoint. The journal consistently publishes outstanding research across various areas within these fields. With an impressive impact factor of 12.3 (2022), Genome Biology has earned its place as the 3rd highest-ranked research journal in the Genetics and Heredity category, according to Thomson Reuters. Additionally, it is ranked 2nd among research journals in the Biotechnology and Applied Microbiology category. It is important to note that Genome Biology is the top-ranking open access journal in this category. In summary, Genome Biology sets a high standard for scientific publications in the field, showcasing cutting-edge research and earning recognition among its peers.