Aptamer engineering of lentiviral vectors for cardiac gene therapies

用于心脏基因治疗的慢病毒载体适体工程

• 批准号: 10759105
• 负责人: George W Jackson
• 金额: $ 28.97万
• 依托单位: BASE PAIR BIOTECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-11 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10759105
• 关键词: Address; Adult; Affect; American; Area; Base Pairing; Binding; Biotechnology; Cardiac; Cardiac Myocytes; Cause of Death; Cell surface; Cells; Clinical; Cost of Illness; DNA; Data Set; Dependovirus; Development; Disease; Dose Limiting; Engineering; Gene Expression; Gene Transduction Agent; Genes; Genetic; Genetic Diseases; Genetic Medicine; Genetic Predisposition to Disease; Genome; Heart; Heart Diseases; Hepatotoxicity; Hypertrophic Cardiomyopathy; Hypertrophy; In Vitro; Individual; Lead; Legal patent; Lentivirus Vector; Libraries; Life; Lilium; Methods; Names; Patients; Persons; Phase; Positioning Attribute; Proteins; RNA; Small Business Innovation Research Grant; Societies; Specificity; Sudden Death; Surface; Techniques; Technology; Testing; Therapeutic; Tissues; Toxic effect; Tropism; Viral Vector; aptamer; clinical candidate; clinical translation; commercialization; curative treatments; delivery vehicle; functional restoration; gene correction; gene delivery system; gene therapy; heart cell; in vivo; inherited cardiomyopathy; innovation; interest; loss of function mutation; novel; overexpression; rational design; receptor; technology platform; translational impact; vector

PROJECT SUMMARY/ABSTRACT Overview: Hypertrophic cardiomyopathy is the leading cause of sudden death in young individuals, where several loss-of-function mutations in key sarcomeric proteins cause hypertrophy. Gene therapy approaches that drive the overexpression of the correct genes can be used to remodel the heart tissue and restore function. However, no gene therapies have been developed for in vivo targeting of the heart to date. A key bottleneck in the field is the ability to engineer advanced viral vectors with prescribed tropism in the patient’s body. Lentiviral vector (LVV) engineering applies rational design principles to define components of the vector envelope, such as attachment proteins, leading to vectors with programmable tissue specificity and off-target activity.

项目概要/摘要 概述：肥厚型心肌病是年轻人猝死的主要原因 个体，其中关键肌节蛋白的几个功能丧失突变导致 基因治疗方法驱动正确的过度表达。 基因可以用来重塑心脏组织并恢复功能，但是没有基因。 迄今为止，已开发出针对心脏的体内靶向疗法。 该领域的能力是设计具有规定向性的先进病毒载体 病人的身体。 慢病毒载体 (LVV) 工程理性应用设计原则来定义 载体包膜的成分，例如附着蛋白，导致载体具有 可编程组织特异性和脱靶活性。