Manipulation of Murine Mitochondrial DNA Heteroplasmy with mtZFNs.
Manipulation of Murine Mitochondrial DNA Heteroplasmy with mtZFNs.
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用 mtZFN 操纵鼠线粒体 DNA 异质性。
DOI：
10.1007/978-1-0716-2922-2_23
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Nash PA
中科院分区：
文献类型：
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作者：
Nash PA
线粒体DNA突变的小鼠模型在开发和优化线粒体基因治疗技术以及在人类试验之前收集临床前数据方面很有希望。它们的适用性源于人类和小鼠线粒体基因组的高度相似性，以及能够选择性转导小鼠组织的合理设计的AAV载体的可用性日益增加。我们的实验室常规优化线粒体靶向锌指核酸酶(MtZFN)，其紧凑性使其非常适合下游基于AAV的体内线粒体基因治疗。本章讨论了对小鼠线粒体基因组进行稳健和精确的基因分型所需的必要预防措施，以及旨在随后在体内使用的mtZFN的优化。
Mouse models of mitochondrial DNA mutations hold promise in the development and optimization of mitochondrial gene therapy technology and for gathering pre-clinical data prior to human trials. Their suitability for this purpose stems from the high similarity of human and murine mitochondrial genomes and the increasing availability of rationally designed AAV vectors capable of selectively transducing murine tissues. Our laboratory routinely optimizes mitochondrially targeted zinc finger nucleases (mtZFNs), the compactness of which makes them highly suitable for downstream AAV-based in vivo mitochondrial gene therapy. This chapter discusses the necessary precautions for the robust and precise genotyping of the murine mitochondrial genome as well as the optimization of mtZFNs intended for subsequent use in vivo.