Diagnosis, Prevention, And Treatment Of Cardiovascular Diseases With Genome Editing

利用基因组编辑诊断、预防和治疗心血管疾病

• 批准号: 10561719
• 负责人: Kiran Musunuru
• 金额: $ 81.25万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-20 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10561719
• 关键词: Address; Cardiovascular Diseases; Cardiovascular system; Caring; Cause of Death; Coronary heart disease; DNA; Data; Diabetes Mellitus; Diagnosis; Disease; Disease model; Genes; Laboratories; Patients; Play; Prevention; Research; Role; Technology; Therapeutic Uses; Untranslated RNA; Variant; cardiovascular disorder risk; clinical sequencing; empowerment; functional genomics; gene function; genome editing; human genomics; insight; lipid metabolism; novel; novel strategies; prevent; therapeutic genome editing; variant of unknown significance

PROJECT SUMMARY For the past 6 years, my independent laboratory has leveraged new approaches in human genomics and pioneered new types of post-genomic functional studies—empowered by genome-editing technologies—to elucidate novel mechanisms that drive cardiovascular diseases. My laboratory has characterized the roles of specific genes involved in lipid metabolism, coronary heart disease, and diabetes, as well yielding insights into how noncoding DNA variation influences the functions of these genes. Going forward, my research will take advantage of recent advances in disease modeling and therapeutic genome editing—advances in which my laboratory played a part—to tackle two exemplary translational challenges in the cardiovascular field: (1) the use of therapeutic genome editing to prevent coronary heart disease, the leading cause of death worldwide; and (2) the use of genome editing to empower high-throughput functional annotation of variants of uncertain significance detected in patients by clinical sequencing.

项目摘要 在过去的6年里，我的独立实验室利用人类基因组学的新方法， 开创了新型的后基因组功能研究-由基因组编辑技术授权- 阐明驱动心血管疾病的新机制。我的实验室已经描述了 参与脂质代谢、冠心病和糖尿病的特定基因，以及对 非编码DNA变异如何影响这些基因的功能。展望未来，我的研究将 疾病建模和治疗性基因组编辑的最新进展的优势-其中我的 实验室发挥了作用-解决了心血管领域的两个典型的翻译挑战：（1） 使用治疗性基因组编辑来预防冠心病，这是导致死亡的主要原因 世界范围内;以及（2）使用基因组编辑来实现变体的高通量功能注释 通过临床测序在患者中检测到的不确定意义。