在ALS小鼠中,RNAi介导的SOD1沉默极大地延长了ALS小鼠的生存和功能结果
Alexandra Weiss1, James W Gilbert2, Iris Valeria Rivera Flores2
1Department of Neurology, UMass Chan Medical School; Worcester, MA, USA, 01605.
概括
一种新型的双价性siRNA有效地抑制了SOD1基因表达在肌缩侧面硬化症 (ALS) 模型中. 这种新疗法可以延长存活时间并减缓疾病的进展,为SOD1相关的ALS提供了改善的治疗潜力.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 药理学 药理学是指药理学的学科.
背景情况:
- 肌缩侧面硬化症 (ALS) 是一种致命的神经退行性疾病.
- 超氧化解突变酶1 (SOD1) 基因的突变导致了家族性和零星ALS病例的很大一部分.
- 突变SOD1蛋白对运动神经元有毒,使SOD1基因抑制成为关键的治疗策略.
研究的目的:
- 开发一种改进的治疗策略,用于SOD1介导的ALS.
- 为有效的SOD1基因抑制创建一个化学稳定双价siRNA (di-siRNA) 支架.
- 在临床前ALS模型中评估di-siRNA的疗效.
主要方法:
- 开发一种针对SOD1.1的化学稳定双价siRNA (di-siRNA).
- 在体外和体内对SOD1表达抑制的评估.
- 在体内对中枢神经系统组织透和SOD1沉默的评估.
- 在SOD1-G93AALS小鼠中静脉内注射di-siRNA.
- 对治疗小鼠的生存,疾病进展和神经病理学的评估.
主要成果:
- 该di-siRNA支架在体外和体内有效抑制了SOD1的表达.
- 优化的化学修饰导致了显著的中枢神经系统组织透和SOD1沉默.
- 在SOD1-G93AALS小鼠中,di-siRNA的静脉内给药延长了超越ASO模式的生存期.
- 在临床前模型中,治疗减缓了疾病进展,减轻了神经病理.
结论:
- 化学稳定的di-siRNA是SOD1介导的ALS的一种有前途的治疗策略.
- 与现有的ASO疗法相比,这种方法提供了改善的药理动力学和药理动力学.
- di-siRNA平台可能适用于其他主要遗传的神经疾病.
更多相关视频
06:49A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS
Published on: October 6, 2015
19.4K
11:46Production of RNA for Transcriptomic Analysis from Mouse Spinal Cord Motor Neuron Cell Bodies by Laser Capture Microdissection
Published on: January 13, 2014
10.6K
相关概念视频
02:15Experimental RNAi
6.0K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.0K
02:30siRNA - Small Interfering RNAs
16.3K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.3K