Insertional mutagenesis by retroviral vectors: current concepts and methods of analysis.

Sean Knight, Mary Collins, Yasuhiro Takeuchi

Research output: Contribution to journalArticlepeer-review


Retroviral vectors derived from gammaretroviruses or lentiviruses have now been used extensively in clinical gene therapy trials for several diseases including primary immunodeficiencies, beta thalassaemia and adrenoleukodystrophy. Their utility in this setting has been readily demonstrated by the largely favourable outcomes in recent clinical trials, however this success has been marred by the emergence of malignancies in some trials. These malignancies were a consequence of perturbation of cellular proto-oncogene expression by the integrated retroviral vectors, the process of which is referred to as ‘insertional mutagenesis’ (IM). In this review, the origins of our understanding of IM are reviewed and applied to the clinical gene therapy trials conducted with retroviral vectors. Old and new methods for assessing this phenomenon are discussed with a view to provide a comprehensive account of this emerging field.
Original languageEnglish
Pages (from-to)211- 227
Number of pages17
JournalCurrent Gene Therapy
Issue number3
Publication statusPublished - Jun 2013


  • Retroviral vector
  • lentiviral vector
  • insertional mutagenesis


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