A Genetic Engineering Toolbox for Marmosets (GETMarm): Development and optimization of genome editing and assisted reproduction techniques for marmoset models

狨猴基因工程工具箱 (GETMarm)：狨猴模型基因组编辑和辅助生殖技术的开发和优化

• 批准号: 10624895
• 负责人: Guoping Feng
• 金额: $ 112.04万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10624895
• 关键词: Acceleration; Alleles; Animals; Area; Assisted Reproductive Technology; Biology; Biopsy Specimen; Brain; Brain Diseases; Breeding; Callithrix; Callithrix jacchus jacchus; Cell model; Chromosomes; Clustered Regularly Interspaced Short Palindromic Repeats; Cryopreservation; Deposition; Development; Diagnostic; Disease model; Embryo; Embryo Transfer; Engineering; Enhancers; Essential Genes; Evaluation; Female; Frequencies; Functional disorder; Gene Frequency; Generations; Genetic; Genetic Engineering; Genetic Models; Genome; Genome engineering; Genotype; Goals; Heterozygote; Human; Injections; Knock-in; Macaca; Methods; Methyl-CpG-Binding Protein 2; Modeling; Modernization; Molecular; Mosaicism; Mus; Neurosciences; Neurosciences Research; Oocytes; Persons; Preimplantation Diagnosis; Primates; Process; Protocols documentation; Reagent; Reproductive Techniques; Research; Resource Sharing; Rett Syndrome; Rodent; Rodent Model; Sexual Maturation; Single Nucleotide Polymorphism; Standardization; Structure; Study models; Synaptic plasticity; System; Technology; Testing; Time; Training; Transposase; United States National Institutes of Health; Work; assisted reproduction; autism spectrum disorder; base editing; base editor; cost; data hub; embryo culture; genetic manipulation; genetic testing; genome editing; improved; in vivo; infancy; model organism; mutant; nonhuman primate; novel; oocyte maturation; prenatal; prime editing; programs; repaired; tool; trait; translational neuroscience; zygote

PROJECT SUMMARY While mice are essential models for many areas of neuroscience, there are also many aspects of higher brain function and dysfunction that cannot be adequately modeled in rodents. Thus, there is a need for new genetic models that have brain structure and function closer to humans. For these reasons, non-human primates (NHP) provide an attractive model to study higher brain function and brain disorders. A promising emerging NHP model is the common marmoset, a small New World primate that has many advantages as a genetic model. Although the adaptation of bacterial CRISPR/Cas systems for targeted genome engineering and model creation has revolutionized modern biology, editing of the marmoset genome is still in its infancy. Given the significant time and money required for marmoset genome editing, new methods to increase editing efficiency, decrease mosaicism, and identify correctly-edited embryos prior to transfer to recipient females are critical. Additionally, new methods for controlling the zygosity of founder animals are necessary to enable analysis of homozygous F0 animals and to avoid homozygous editing when targeting essential genes that cause embryonic lethality upon biallelic disruption. To these ends, we propose a research program that will significantly enhance our ability to introduce multiple types of edits into the marmoset genome, reduce mosaicism, control the zygosity of edits, and identify successfully edited embryos through prenatal genetic testing. We will disseminate these technologies and models through direct resource sharing, in-person trainings, deposition to NIH-supported Marmoset Coordination Center. Together, the proposed advances will significantly reduce the time, effort, costs and animal numbers necessary to marmoset genetic models and will unlock the true potential of marmosets for basic and translational neuroscience research.

项目总结