Abstract：
Leucine-rich repeat kinase 2 (LRRK2) gene mutation is an autosomal dominant mutation associated with Parkinson\'s disease (PD). Among LRRK2 gene mutations, the LRRK2 G2019S mutation is frequently involved in PD onset. Currently, diverse gene correction tools such as zinc finger nucleases (ZFNs), helper-dependent adenoviral vector (HDAdV), the bacterial artificial chromosome-based homologous recombination (BAC-based HR) system, and CRISPR/Cas9-homology-directed repair (HDR) or adenine base editor (ABE) are used in genome editing. Gene correction of the LRRK2 G2019S mutation has been applied whenever new gene therapy tools emerge, being mainly applied to induced pluripotent stem cells (LRRK2 G2019S-mutant iPSCs). Here, we comprehensively introduce the principles and methods of each programmable nuclease such as ZFN, CRISPR/Cas9-HDR or ABE applied to LRRK2 G2019S, as well as those of HDAdV or BAC-based HR systems used as nonprogrammable nuclease systems.
摘要：
富含亮氨酸重复序列激酶2(LRRK2)基因突变是一种与帕金森病(PD)相关的常染色体显性突变。在LRRK2基因突变中，LRRK2G2019S突变经常参与PD的发病。目前,多种基因校正工具，如锌指核酸酶(ZFN)，辅助依赖性腺病毒载体（HDAdV），基于细菌人工染色体的同源重组（基于BAC的HR）系统，和CRISPR/Cas9同源定向修复(HDR)或腺嘌呤碱基编辑器(ABE)用于基因组编辑。每当新的基因治疗工具出现时，LRRK2G2019S突变的基因校正已被应用，主要应用于诱导多能干细胞（LRRK2G2019S-突变体iPSCs）。这里,我们全面介绍了ZFN等每种可编程核酸酶的原理和方法，CRISPR/Cas9-HDR或ABE应用于LRRK2G2019S，以及用作非可编程核酸酶系统的基于HDAdV或BAC的HR系统。
