Abstract
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.
Keywords: Retroviral vector, lentiviral vector, insertional mutagenesis.
Current Gene Therapy
Title:Insertional Mutagenesis by Retroviral Vectors: Current Concepts and Methods of Analysis
Volume: 13 Issue: 3
Author(s): Sean Knight, Mary Collins and Yasuhiro Takeuchi
Affiliation:
Keywords: Retroviral vector, lentiviral vector, insertional mutagenesis.
Abstract: 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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Cite this article as:
Knight Sean, Collins Mary and Takeuchi Yasuhiro, Insertional Mutagenesis by Retroviral Vectors: Current Concepts and Methods of Analysis, Current Gene Therapy 2013; 13 (3) . https://dx.doi.org/10.2174/1566523211313030006
DOI https://dx.doi.org/10.2174/1566523211313030006 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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