title: Effect of the internal promoter on insertional gene activation by lentiviral vectors with an intact HIV long terminal repeat.
abstract: 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.
authors.affiliation: Division of Infection and Immunity, University College London, 46 Cleveland St., London W1T 4JF, United Kingdom.
authors.forename: Sean
authors.initials: S
authors.lastname: Knight
authors.forename: Marieke
authors.initials: M
authors.lastname: Bokhoven
authors.forename: Mary
authors.initials: M
authors.lastname: Collins
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeuchi
mesh_terms: D002460:Cell Line; D020869:Gene Expression Profiling; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D016254:Mutagenesis, Insertional; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D015533:Transcriptional Activation