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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)
Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Role of Neural Stem Cells in Parkinsons Disease
Current Signal Transduction Therapy Transcription Factor NF-κB Inhibitors as Single Therapeutic Agents or in Combination with Classical Chemotherapeutic Agents for the Treatment of Hematologic Malignancies
Current Molecular Pharmacology The Dark Side of Stem Cells: Triggering Cancer Progression by Cell Fusion
Current Molecular Medicine Blockade of Insulin-Like Growth Factor Type-1 Receptor with Cixutumumab (IMC-A12): A Novel Approach to Treatment for Multiple Cancers
Current Drug Targets Sources of β-Cells for Cell Therapy in Diabetes
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) NF-κB Activation by FcεRI-Mediated Signal Transduction
Current Immunology Reviews (Discontinued) Present, Emerging and Possible Future Biomarkers in Castration Resistant Prostate Cancer (CRPC)
Current Cancer Drug Targets Th1-mediated Pathology in Mouse Models of Human Disease is Ameliorated by Concurrent Th2 Responses to Parasite Antigens
Current Topics in Medicinal Chemistry Effects of Iron Chelation in Osteosarcoma
Current Cancer Drug Targets The Molecular Basis of Herpesviruses as Oncolytic Agents
Current Pharmaceutical Biotechnology Procarbazine – A Traditional Drug in the Treatment of Malignant Gliomas
Current Medicinal Chemistry Serum Proteomics in the Diagnosis and Treatment of Haematological Malignancies
Current Proteomics Progress in the Preclinical Discovery and Clinical Development of Class I and Dual Class I/IV Phosphoinositide 3-Kinase (PI3K) Inhibitors
Current Medicinal Chemistry Diazenyl Derivatives as Therapeutic and Diagnostic Agents Acting on Central Nervous System
Central Nervous System Agents in Medicinal Chemistry Quantitative Proteomics in the Study of Phosphotyrosine-Mediated Signal Transduction Pathway
Current Proteomics DNA Methylation Leaves Its Mark in Head and Neck Squamous Cell Carcinomas (HNSCC)
Current Genomics The Use of Infliximab in Dermatology
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Graphical Abstracts:
Current Organic Chemistry Which Dose of Folic Acid Should Pregnant Diabetic Women Receive?
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Direct Modification of Bioactive Phenothiazines by Exposure to Laser Radiation
Recent Patents on Anti-Infective Drug Discovery