Aptamer engineering of lentiviral vectors for cardiac gene therapies

项目摘要/摘要 概述：肥厚型心肌病是年轻人猝死的主要原因 个体，其中关键肌瘤蛋白的几个功能丧失突变导致 肥大。驱动正确基因过度表达的基因治疗方法 基因可以用来重塑心脏组织和恢复功能。然而，没有基因 到目前为止，已经开发出体内靶向心脏的治疗方法。一个关键的瓶颈 在这一领域，有能力设计出具有规定取向的高级病毒载体 病人的身体。 慢病毒载体(LVV)工程应用合理设计原则来定义 载体包膜的组成部分，如附着蛋白，导致载体具有 可编程的组织特异性和非靶标活性。

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.