相关实验视频

Updated: Jun 3, 2025

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells

Published on: May 30, 2025

双重定位的CRISPR-CasRx在体外和体内减少C9orf72ALS/FTD感觉和反感觉重复RNA

Liam Kempthorne^1,2, Deniz Vaizoglu^1,2, Alexander J Cammack^1,2

¹UK Dementia Research Institute at UCL, London, WC1E 6BT, UK.

Nature communications

|January 8, 2025

概括

一个新的CRISPR-Cas13d系统,CasRx,有效地减少了C9orf72基因扩张的有毒RNA和蛋白质副产品. 这种RNA向性疗法在治疗前性痴呆症 (FTD) 和肌缩性侧面硬化症 (ALS) 中表现有前途.

科学领域:

神经科学是一个神经科学.
遗传学是一个遗传学.
分子生物学分子生物学
在RNA治疗方面,RNA疗法.

背景情况:

C9orf72 G4C2重复扩张是前性痴呆症 (FTD) 和肌性侧面硬化症 (ALS) 最常见的遗传原因.
这种扩张导致有毒的感觉和反感觉重复RNA和二重复蛋白 (DPR),有助于疾病病理.
针对来自两个重复链的RNA和蛋白质物种是潜在的治疗策略.

研究的目的:

评估CRISPR-Cas13d变体CasRx在减少C9orf72重复转录和DPR中的有效性.
评估CasRx在C9orf72相关的ALS/FTD的细胞和动物模型中的治疗潜力.

主要方法:

利用CRISPR-Cas13d变体CasRx来准C9orf72的感觉和反感觉重复转录.
在HEK细胞中测试了CasRx与过度表达的C9orf72重复,患者衍生的iPSC-神经元线和C9orf72重复的小鼠模型.
评估了重复RNA和DPR的减少,以及对刺激毒性的保护.

主要成果:

CasRx有效地降低了HEK细胞中的感觉和反感觉C9orf72重复转录和DPR.
在患者衍生的神经元中,CasRx降低了内源性重复RNA和DPR,减轻了谷氨酸诱导的兴奋毒性.
在两种C9orf72小鼠模型中,AAV介导的CasRx输送显著减少了重复含有的转录.

结论:

CRISPR-Cas13d系统CasRx对C9orf72重复转录和相关的有毒蛋白质表现出强烈的活性.
向RNA的CRISPR系统代表了C9orf72相关的肌缩侧面硬化症和前性痴呆症的有前途的治疗途径.
在C9orf72 ALS/FTD中,CasRx提供了一种潜在的策略,可以同时针对多种致病物种.

更多相关视频

Ubiquitous and Tissue-specific RNA Targeting in Drosophila Melanogaster using CRISPR/CasRx

Ubiquitous and Tissue-specific RNA Targeting in Drosophila Melanogaster using CRISPR/CasRx

Published on: February 5, 2021

CIRCLE-Seq for Interrogation of Off-Target Gene Editing

CIRCLE-Seq for Interrogation of Off-Target Gene Editing

Published on: November 1, 2024

相关概念视频

CRISPR

CRISPR

Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...

CRISPR and crRNAs

CRISPR and crRNAs

Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...