Genetic Engineering Core

基因工程核心（GEC）项目摘要 基因工程核心的总体目标是支持MARMO-AD的需求 通过提供以下服务：（1）使用CRISPR/Cas9基因编辑对绒猴进行遗传工程改造， (2)开发和优化绒猴生殖系基因编辑的使能技术，以及（3） 创建成纤维细胞系并将其分化为诱导神经干细胞和神经元。 普通绒猴（Callithrix jacchus）是一种新世界的非人类灵长类动物， 在生物医学研究中的实际优势，并迅速成为一个备受追捧的模式 神经科学界的生物。对绒猴的迅速欣赏 神经生物学与基因编辑技术的同期进展协同作用， 使绒猴成为了非人类灵长类的基因工程动物， 大脑功能和研究大脑疾病，如阿尔茨海默病。GEC将提供 使用CRISPR/Cas9基因编辑生产新型基因工程所需的所有服务 携带人类早发型和晚发型阿尔茨海默病高风险等位基因的绒猴。 在创造这些基因编辑动物的同时，GEC将同时开发和优化 实现高效种系基因编辑的技术。这些新技术包括 刺激卵巢以提高成熟绒猴卵母细胞产生的方法， 减少基因编辑的绒猴中嵌合现象的方法。技术进步将减少 降低了成本，加快了生产基因工程绒猴的速度 同时也减少了动物的数量。最后，GEC将产生绒猴成纤维细胞系 并将其分化为诱导的神经干细胞和神经元。细胞系将用于 创建DNA测序文库并用于体外表型表征基因编辑 支持项目目标的动物。

PROJECT SUMMARY GENETIC ENGINEERING CORE (GEC) The overall goal of the Genetic Engineering Core (GEC) is to support the needs of MARMO-AD by providing services to (1) genetically engineer marmosets using CRISPR/Cas9 gene editing, (2) develop and optimize enabling technologies for germline gene editing in marmoset, and (3) create fibroblast cell lines and differentiate them into induce neuronal stem cells and neurons. The common marmoset (Callithrix jacchus) is a New World non-human primate with numerous practical advantages in biomedical research and is quickly becoming a much sought-after model organism by the neuroscience community. The rapidly growing appreciation of marmoset neurobiology is synergizing with contemporaneous advances in gene editing techniques to make marmosets the genetically engineered non-human primate of choice for understanding brain function and to study brain disorders such as Alzheimer’s Disease. The GEC will provide all services required to use CRISPR/Cas9 gene editing to produce novel genetically engineered marmosets that harbor human high-risk alleles for early and late onset Alzheimer’s disease. While creating these gene-edited animals, the GEC will simultaneously develop and optimize enabling technologies for efficient germline gene editing. These technologies include novel methods of ovarian stimulation to enhance production of mature marmoset oocytes, and novel approaches to reduce mosaicism in gene edited marmosets. Improved technologies will reduce the cost and increase the speed at which genetically engineered marmosets can be produced while also reducing animal numbers. Lastly, the GEC will produce marmoset fibroblast cell lines and differentiate them into induced neuronal stem cells and neurons. Cell lines will be used to create DNA sequencing libraries and for in vitro phenotypic characterization of gene edited animals in support of the Project goals.