Insertional Mutagenesis by Retroviral Vectors: Current Concepts and Methods of Analysis
Sean Knight, Mary Collins and Yasuhiro Takeuchi
Affiliation: MRC/UCL Centre for Medical Molecular Virology and Wohl Virion Centre, Division of Infection & Immunity, UCL Cancer Institute, University College London, London, UK.
Keywords: Retroviral vector, lentiviral vector, insertional mutagenesis.
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.
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