基因治疗慢病毒载体的转导增强策略

Enhancing Lentiviral Vector Transduction Efficiency for Facilitating Gene Therapy

基于慢病毒载体的体外基因治疗已在临床试验中取得良好的效果,有望治愈一些造血系统的单基因遗传病。通过提高靶细胞转导效率和减少转导中病毒载体量,基因治疗有效性、安全性和成本都可以得到改善。不同包膜糖蛋白伪型慢病毒载体通过与细胞膜表面的不同受体结合,促进病毒黏附和入胞,增强不同靶细胞的病毒转导效率。此外病毒转导增强剂可以在病毒进入细胞过程或进入后发挥作用,在提高转导效率的同时使靶转导基因在体内长期稳定表达。通过对这两类方法的总结回顾,旨在为慢病毒载体的转导效率提供新的优化策略,使基因治疗得到更广泛的应用。

Lentiviral vectors(LVVs)are used for various gene therapeutic applications in vitro,and have shown very promising results in several clinical trials.This possibility of a durable cure for monogenic diseases affecting the hematopoietic system has made gene therapy very attractive.Yet,efficiency,safety,and cost of LVVs gene therapy could be ameliorated by enhancing target cell transduction levels and reducing the amount of LVVs used on the cells.LVVs are pseudotyped with different viral envelope glycoproteins to alter and improve their tropism for different target cells.Another strategy to optimize the entry and post-entry steps of LVVs is the addition of transduction enhancers(TEs)during the transduction procedure,which improves the transduction efficiency and keeps stable expression of transferred genes in vivo.The combination of pseudotyping with heterologous viral envelopes and adding TEs increased the transduction efficiency of LVVs,and has the potential to improve clinical protocols.