Abstract
Lentiviral vectors are among the most efficient gene transfer tools for dividing and non-dividing cells. However, insertional mutagenesis has been observed in clinical trials with oncoretroviral vectors and this has prompted detailed study of genotoxicty of all integrating vectors. For many applications, avoiding integration is the most straightforward approach to overcome this problem and is facilitated by the extensive studies of the integrating mechanisms of lentiviruses. Indeed, non-integrating lentiviral vectors have been developed by mutating the integrase gene or by modifying the attachment sequences of the LTRs. In this review, we first consider on the toxicity associated with integration and on lentivirus integrase biology, and discuss the implications of integrase mutant studies for the development of non-integrating lentiviral vectors. We review published data concerning non-integrating lentiviral vectors with particular focus on their residual integration and transgene expression efficiency. Finally, the latest advances in the development of genetic engineering tools derived from non-integrating lentiviral vectors are presented.
Keywords: HIV, integrase, episome, genotoxicity, gene therapy, gene editing, site-specific recombinase, biosafety
Current Gene Therapy
Title: Non-Integrating Lentiviral Vectors
Volume: 8 Issue: 6
Author(s): Chamsy Sarkis, Stephanie Philippe, Jacques Mallet and Che Serguera
Affiliation:
Keywords: HIV, integrase, episome, genotoxicity, gene therapy, gene editing, site-specific recombinase, biosafety
Abstract: Lentiviral vectors are among the most efficient gene transfer tools for dividing and non-dividing cells. However, insertional mutagenesis has been observed in clinical trials with oncoretroviral vectors and this has prompted detailed study of genotoxicty of all integrating vectors. For many applications, avoiding integration is the most straightforward approach to overcome this problem and is facilitated by the extensive studies of the integrating mechanisms of lentiviruses. Indeed, non-integrating lentiviral vectors have been developed by mutating the integrase gene or by modifying the attachment sequences of the LTRs. In this review, we first consider on the toxicity associated with integration and on lentivirus integrase biology, and discuss the implications of integrase mutant studies for the development of non-integrating lentiviral vectors. We review published data concerning non-integrating lentiviral vectors with particular focus on their residual integration and transgene expression efficiency. Finally, the latest advances in the development of genetic engineering tools derived from non-integrating lentiviral vectors are presented.
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Cite this article as:
Sarkis Chamsy, Philippe Stephanie, Mallet Jacques and Serguera Che, Non-Integrating Lentiviral Vectors, Current Gene Therapy 2008; 8 (6) . https://dx.doi.org/10.2174/156652308786848012
DOI https://dx.doi.org/10.2174/156652308786848012 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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