Lentivirus-mediated reprogramming of somatic cells in the absence of transgenic transcription factors

Nicole M Kane, Ali Nowrouzi, Sayandip Mukherjee, Michael P Blundell, Jenny A Greig, Wai Kwong Lee, Miles D Houslay, Graeme Milligan, Joanne C Mountford, Christof von Kalle, Manfred Schmidt, Adrian J Thrasher, Andrew H Baker

Research output: Contribution to journalArticlepeer-review

Abstract

Retroviral vectors remain the most efficient and widely applied system for induction of pluripotency. However, mutagenic effects have been documented in both laboratory and clinical gene therapy studies, principally as a result of dysregulated host gene expression in the proximity of defined integration sites. Here, we report that cells with characteristics of pluripotent stem cells can be produced from normal human fibroblasts in the absence of reprogramming transcription factors (TFs) during lentiviral (LV) vector-mediated gene transfer. This occurred via induced alterations in host gene and microRNA (miRNA) expression and detrimental changes in karyotype. These findings demonstrate that vector-induced genotoxicity may alone play a role in somatic cell reprogramming derivation and urges caution when using integrating vectors in this setting. Clearer understanding of this process may additionally reveal novel insights into reprogramming pathways.

Original languageEnglish
Pages (from-to)2139-45
Number of pages7
JournalMolecular Therapy
Volume18
Issue number12
DOIs
Publication statusPublished - Dec 2010

Keywords

  • Cellular Reprogramming
  • Fibroblasts
  • Gene Expression Profiling
  • Humans
  • Lentivirus
  • MicroRNAs
  • Pluripotent Stem Cells
  • Transcription Factors

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