Abstract：
Lentiviral vector (LVV) has been used as one of the common carriers for gene therapy in clinical trials. LVV-mediated clinical trials have being reported in successfully treating hundreds of β-thalassemia cases. These LVVs bear an inversely placed β-hemoglobin (HBB) gene expression cassette for preserving introns during the viral RNA packaging. Consequently, these LVVs often produce a small amount of negatively orientated transcript driven by its internal gene promoter and would lower the viral titer by the minus-strand complemented with the viral backbone. To overcome this problem, we designed shRNAs specifically target the minus-strand RNA driven by the LVV internal promoter that resulted in a notable increase in the viral titer. This report demonstrates a simple and positive mean for increasing the effectiveness for gene therapy with the LVV system.
摘要：
慢病毒载体（LVV）已被用作临床试验中基因治疗的常见载体之一。已经报道了LVV介导的临床试验成功治疗了数百个β-地中海贫血病例。这些LVV带有反向放置的β-血红蛋白(HBB)基因表达盒,用于在病毒RNA包装期间保存内含子。因此,这些LVV通常产生少量由其内部基因启动子驱动的负取向转录物,并且通过与病毒骨架互补的负链降低病毒滴度。为了克服这个问题，我们设计了特异性靶向由LVV内部启动子驱动的负链RNA的shRNA,其导致病毒滴度显著增加.该报告证明了提高LVV系统基因治疗有效性的简单而积极的手段。
