IN UTERO SMALL AND LARGE ANIMAL RESOURCE CORE

子宫内小型和大型动物资源核心

• 批准号: 10668617
• 负责人: Alan W. Flake
• 金额: $ 106.93万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10668617
• 关键词: Animal Model; Animals; Biodistribution; Birth; Cell Therapy; Clinical Research; Data; Disease; Dose; Early treatment; Fetal Sheep; Fetal safety; Fetus; Future; Gene Delivery; Genes; Growth; Harvest; Human; Immune response; Immune system; Injections; Knowledge; Lead; Letters; Liver; Macaca fascicularis; Mendelian disorder; Metabolic Diseases; Modeling; Morbidity - disease rate; Mothers; Mucopolysaccharidosis I; Mus; Onset of illness; Organ; Pathology; Personal Satisfaction; Pregnancy; Preparation; Procedures; Property; Proteins; Publishing; Research Personnel; Resources; Safety; Services; Sheep; Structure of omphalomesenteric vein; Technical Expertise; Techniques; Technology; Therapeutic; Time; Tissue Harvesting; Tissues; Toxic effect; Tyrosinemias; Umbilical vein; Weight; animal resource; base editing; base editor; cisterna magna; delivery vehicle; design; effective therapy; efficacy evaluation; experience; fetal; gene therapy; genome editing; hepatic vein; in utero; in vivo; information gathering; lipid nanoparticle; maternal safety; maternal serum; maternal wellbeing; mortality; mouse model; nanoparticle delivery; nonhuman primate; postnatal; preclinical study; prenatal; sheep model; stem cells; therapeutic genome editing; ultrasound

PROJECT SUMMARY Many monogenic diseases strike prior to or soon after birth and cause significant morbidity and mortality. In utero genome editing (IUGE) takes advantage of normal fetal properties, including small size, abundant progenitor cells, and immature immune system, to safely and efficiently institute the genome editing therapeutic prior to the onset of pathology. To fully understand the potential of IUGE and in preparation for IND applications, rigorous small and large animal studies are required to assess efficacy as well as fetal and maternal safety. The In Utero Small and Large Animal Resource Core will provide the knowledge and technical expertise required to design, implement and analyze in vivo gene editing therapies in mouse and large animal fetal models, including nonhuman primates.

项目摘要 许多单基因疾病在出生前或出生后不久发作，并造成严重的发病率和死亡率。在子宫内 基因组编辑（IUGE）利用了正常胎儿的特性，包括小尺寸，丰富的祖细胞， 细胞和不成熟的免疫系统，以安全和有效地研究基因组编辑治疗之前， 病理学的开始。为了充分了解IUGE的潜力，并为IND申请做准备， 需要进行小型和大型动物研究以评估功效以及胎儿和母体安全性。的In 小型和大型动物资源中心将提供所需的知识和技术专长， 在小鼠和大型动物胎儿模型中设计、实施和分析体内基因编辑疗法，包括 非人类灵长类动物