Hirata Maki, Wittayarat Manita, Namula Zhao, Anh Le Quynh, Lin Qingyi, Takebayashi Koki, Thongkittidilok Chommanart, Tanihara Fuminori, Otoi Takeshige
Faculty of Bioscience and Bioindustry, Tokushima University, Tokushima 770-8501, Japan.
Faculty of Veterinary Science, Prince of Songkla University, Songkhla 90110, Thailand.
Animals (Basel). 2021 Feb 23;11(2):578. doi: 10.3390/ani11020578.
Liposome-mediated gene transfer has become an alternative method for establishing a gene targeting framework, and the production of mutant animals may be feasible even in laboratories without specialized equipment. However, how this system functions in mammalian oocytes and embryos remains unclear. The present study was conducted to clarify whether blastocyst genome editing can be performed by treatment with lipofection reagent, guide RNA, and Cas9 for 5 h without using electroporation or microinjection. A mosaic mutation was observed in blastocysts derived from zona pellucida (ZP)-free oocytes following lipofection treatment, regardless of the target genes. When lipofection treatment was performed after in vitro fertilization (IVF), no significant differences in the mutation rates or mutation efficiency were found between blastocysts derived from embryos treated at 24 and 29 h from the start of IVF. Only blastocysts from embryos exposed to lipofection treatment at 29 h after IVF contained biallelic mutant. Furthermore, there were no significant differences in the mutation rates or mutation efficiency between blastocysts derived from embryos at the 2- and 4-cell stages. This suggests that lipofection-mediated gene editing can be performed in ZP-free oocytes and ZP-free embryos; however, other factors affecting the system efficiency should be further investigated.
脂质体介导的基因转移已成为建立基因靶向框架的一种替代方法,即使在没有专门设备的实验室中生产突变动物也可能是可行的。然而,该系统在哺乳动物卵母细胞和胚胎中的作用机制仍不清楚。本研究旨在阐明是否可以通过用脂质转染试剂、引导RNA和Cas9处理5小时来进行囊胚基因组编辑,而无需使用电穿孔或显微注射。无论目标基因如何,在脂质转染处理后的无透明带(ZP)卵母细胞来源的囊胚中均观察到嵌合突变。当在体外受精(IVF)后进行脂质转染处理时,从IVF开始24小时和29小时处理的胚胎来源的囊胚之间,突变率或突变效率没有显著差异。只有IVF后29小时接受脂质转染处理的胚胎来源的囊胚含有双等位基因突变体。此外,2细胞期和4细胞期胚胎来源的囊胚之间的突变率或突变效率没有显著差异。这表明脂质转染介导的基因编辑可以在无ZP的卵母细胞和无ZP的胚胎中进行;然而,影响该系统效率的其他因素应进一步研究。