在Duchenne肌肉发育不良的小鼠模型中改善基因组编辑
Christopher E Nelson1, Chady H Hakim2, David G Ousterout1
1Department of Biomedical Engineering, Duke University, Durham, NC, USA. Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
Science (New York, N.Y.)
|January 2, 2016
概括
在MDX小鼠中,CRISPR-Cas9基因组编辑成功地删除了肌肉缩的模型 - - 肌肉缩基因的突变前体. 这种方法恢复了功能性消毒蛋白和改善肌肉功能,为DMD提供了潜在的治疗方法.
科学领域:
- 生物技术
- 遗传学
- 分子生物学
背景情况:
- 杜申肌肉发育不良 (DMD) 是一种严重的遗传性疾病,由发育不良基因突变引起,大约每5000名男性中就有1名受影响.
- 目前对DMD的治疗策略有限,强调需要创新的治疗方法.
研究的目的:
- 研究CRISPR-Cas9基因组编辑治疗杜申肌肉衰竭的潜力.
- 在DMD动物模型中评估从基因中移除突变的23元的有效性.
主要方法:
- 使用腺相关病毒 (AAV) 将CRISPR- Cas9系统输入DMD的mdx小鼠模型.
- 在成年小鼠和新生儿中,使用CRISPR- Cas9精确删除基因的第23个外基因,测试了局部和全身传递方法.
主要成果:
- 使用CRISPR-Cas9成功删除了双基因中的第23个外基因.
- 在骨和心脏肌肉中观察到修改后的基因表达的恢复和功能性基因蛋白的部分恢复.
- 在肌肉生化和肌肉力量方面有显著的改善.
结论:
- 基于CRISPR-Cas9的基因组编辑显示了杜申肌肉发育不良的显著治疗潜力.
- 这项研究为开发基因组编辑疗法提供了坚实的基础,
相关概念视频
01:21Satellite Stem Cells and Muscular Dystrophy
2.6K
Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...
2.6K
01:16In-vitro Mutagenesis
17.6K
To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
17.6K