Nonhuman primates (NHPs), which are closely related to humans, are useful in biomedical research, and an increasing number of NHP disease models have been reported using gene editing. However, many disease-related genes cause perinatal death when manipulated homozygously by gene editing. In addition, NHP resources, which are limited, should be efficiently used. Here, to address these issues, we developed a method of introducing heterozygous genetic modifications into common marmosets by combining Platinum transcription activator-like effector nuclease (TALEN) and a gene-editing strategy in oocytes. We succeeded in introducing the heterozygous exon 9 deletion mutation in the presenilin 1 gene, which causes familial Alzheimer’s disease in humans, using this technology. As a result, we obtained animals with the expected genotypes and confirmed several Alzheimer’s disease-related biochemical changes. This study suggests that highly efficient heterozygosity-oriented gene editing is possible using TALEN and oocytes and is an effective method for producing genetically modified animals.

非人类灵长类动物（NHP）与人类密切相关，在生物医学研究中很有用，并且越来越多的NHP疾病模型被报道使用基因编辑。然而，当通过基因编辑进行纯合操作时，许多与疾病相关的基因会导致围产期死亡。此外，NHP资源有限，应得到有效利用。在这里，为了解决这些问题，我们开发了一种通过结合铂类转录激活因子效应核酸酶（TALEN）和卵母细胞基因编辑策略将杂合基因修饰引入普通狨猴的方法。利用这项技术，我们成功地在早老素 1 基因中引入杂合外显子 9 缺失突变，该基因会导致人类家族性阿尔茨海默病。结果，我们获得了具有预期基因型的动物，并证实了一些与阿尔茨海默病相关的生化变化。这项研究表明，使用 TALEN 和卵母细胞进行高效的杂合性基因编辑是可能的，并且是生产转基因动物的有效方法。