通过基因组编辑选择性消除生殖系中的线粒体突变
Pradeep Reddy1, Alejandro Ocampo1, Keiichiro Suzuki1
1Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Cell
|April 25, 2015
概括
研究人员开发了一种方法,通过消除生殖细胞中突变的线粒体DNA (mtDNA) 来预防线粒体疾病. 这种技术转移mtDNA异质体,为遗传遗传性疾病提供潜在的治疗方法.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 生殖医学 生殖医学
背景情况:
- 线粒体疾病是由线粒体DNA (mtDNA) 突变引起的母性遗传遗传疾病.
- 大多数患者表现出mtDNA异质体,即突变和野生类型mtDNA的共存.
- 防止这些疾病的生殖系传播是一个重大挑战.
研究的目的:
- 开发和展示一种预防线粒体疾病的生殖系传播的策略.
- 通过选择性地消除突变的mtDNA来诱导mtDNA异质体的转变.
- 建立一种潜在的治疗方法来治疗遗传性线粒体疾病.
主要方法:
- 在NZB/BALB异oplasmic小鼠中利用线粒体向的限制性内核酶和TALEN,以防止生殖系传播.
- 应用针对线粒体的TALENs (mito-TALENs) 来降低哺乳动物卵细胞中突变的人类mtDNA水平.
- 针对性特定突变,负责勒伯遗传性视神经病变 (LHON) 和神经性肌肉衰弱,动脉缩和视网膜色素炎 (NARP).
主要成果:
- 在异质体小鼠中成功阻止了mtDNA单元型的生殖系传播.
- 在卵细胞中显著降低了与LHON和NARP相关的突变人类mtDNA水平.
- 验证了 mito-TALENs 在选择性消除突变 mtDNA 的疗效.
结论:
- 开发的战略为预防线粒体疾病的跨代遗传提供了一个潜在的治疗途径.
- 通过工程核酶选择性消除突变mtDNA可以纠正mtDNA异质.
- 这种方法对未来针对遗传性线粒体疾病的干预有希望.
相关概念视频
02:59Animal Mitochondrial Genetics
10.1K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
10.1K
01:16In-vitro Mutagenesis
17.7K
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.
17.7K
01:59CRISPR
60.2K
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...
60.2K
01:28CRISPR/Cas9 Genome Editing
3.1K
The CRISPR-Cas system serves as a bacterial defense mechanism against invading genetic elements such as viruses and plasmids, forming the foundation for its adaptation as a powerful genome-editing tool. Originally discovered in prokaryotes, this system has been repurposed to revolutionize genetic engineering across a wide range of organisms, including plants, animals, and humans. The core component, Cas9, is an endonuclease derived from Streptococcus pyogenes, capable of introducing...
3.1K
01:39Mutations
98.2K
Overview
98.2K