Division of Infection and Immunity, University College London, 46 Cleveland St., London W1T 4JF, United Kingdom.
J Virol. 2010 May;84(9):4856-9. doi: 10.1128/JVI.02476-09. Epub 2010 Feb 24.
Insertional mutagenesis by viral vectors is a problem in gene therapy. We recently reported that lentiviral vectors with an intact HIV long terminal repeat (LTR) caused insertional gene activation by transcripts from the 5' LTR splicing to an adjacent gene. Here we demonstrate that the level of transcription from the 5' LTR, and also insertional gene activation, is dependent on the internal promoter in the vector. We also show that there are more transcripts originating from the 5' LTR than from, or reading through, the 3' LTR. This study will allow the design of safer lentiviral vectors for applications in which an intact HIV LTR is required.
病毒载体的插入突变是基因治疗中的一个问题。我们最近报道，带有完整 HIV 长末端重复序列（LTR）的慢病毒载体通过从 5' LTR 剪接到相邻基因的转录物引起插入基因激活。在这里，我们证明了来自 5' LTR 的转录水平，以及插入基因激活，依赖于载体中的内部启动子。我们还表明，来自 5' LTR 的转录物比来自 3' LTR 的转录物或通读 3' LTR 的转录物更多。这项研究将允许设计更安全的慢病毒载体，用于需要完整 HIV LTR 的应用。
