Abstract
There have been major changes since the incidents of leukemia development in X-SCID patients after the treatments using retroviral gene therapy. Due to the risk of oncogenesis caused by retroviral insertional activation of host genes, most of the efforts focused on the lentiviral therapies. However, a relative clonal dominance was detected in a patient with β-thalassemia Major, two years after the subject received genetically modified hematopoietic stem cells using lentiviral vectors. This disappointing result of the recent clinical trial using lentiviral vector tells us that the current and most advanced vector systems does not have enough safety. In this review, various safety features that have been tried for the retroviral gene therapy are introduced and the possible new ways of improvements are discussed. Additional feature of chromatin insulators, co-transduction of a suicidal gene under the control of an inducible promoter, conditional expression of the transgene only in appropriate target cells, targeted transduction, cell type-specific expression, targeted local administration, splitting of the viral genome, and site specific insertion of retroviral vector are discussed here.
Keywords: Retroviral, Gene, Therapy, Safety, Insertional, Targeted, Vectors, Insulator, transgene, target cells
Current Gene Therapy
Title: Current Advances in Retroviral Gene Therapy
Volume: 11 Issue: 3
Author(s): Youngsuk Yi, Moon Jong Noh and Kwan Hee Lee
Affiliation:
Keywords: Retroviral, Gene, Therapy, Safety, Insertional, Targeted, Vectors, Insulator, transgene, target cells
Abstract: There have been major changes since the incidents of leukemia development in X-SCID patients after the treatments using retroviral gene therapy. Due to the risk of oncogenesis caused by retroviral insertional activation of host genes, most of the efforts focused on the lentiviral therapies. However, a relative clonal dominance was detected in a patient with β-thalassemia Major, two years after the subject received genetically modified hematopoietic stem cells using lentiviral vectors. This disappointing result of the recent clinical trial using lentiviral vector tells us that the current and most advanced vector systems does not have enough safety. In this review, various safety features that have been tried for the retroviral gene therapy are introduced and the possible new ways of improvements are discussed. Additional feature of chromatin insulators, co-transduction of a suicidal gene under the control of an inducible promoter, conditional expression of the transgene only in appropriate target cells, targeted transduction, cell type-specific expression, targeted local administration, splitting of the viral genome, and site specific insertion of retroviral vector are discussed here.
Export Options
About this article
Cite this article as:
Yi Youngsuk, Jong Noh Moon and Hee Lee Kwan, Current Advances in Retroviral Gene Therapy, Current Gene Therapy 2011; 11 (3) . https://dx.doi.org/10.2174/156652311795684740
DOI https://dx.doi.org/10.2174/156652311795684740 |
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
-
Combination Treatment of p53-Null HL-60 cells with Histone Deacetylase Inhibitors and Chlorambucil Augments Apoptosis and Increases BCL6 and p21 Gene Expression
Current Molecular Pharmacology NADPH Oxidases NOXs and DUOXs as Putative Targets for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Vybrant DyeCycle Violet Stain Discriminates Two Different Subsets of CD34+ Cells
Current Stem Cell Research & Therapy Microwave-assisted Cycloaddition Reactions in Carbo- and Heterocyclic Chemistry
Current Organic Chemistry Importance of Influx and Efflux Systems and Xenobiotic Metabolizing Enzymes in Intratumoral Disposition of Anticancer Agents
Current Cancer Drug Targets Interplay between Epigenetics & Cancer Metabolism
Current Pharmaceutical Design Culture Supernatants from Lactobacillus plantarum Induce Necrosis on a Human Promyelocytic Leukemia Cell Line
Endocrine, Metabolic & Immune Disorders - Drug Targets Oncogenic MicroRNAs in the Genesis of Leukemia and Lymphoma
Current Pharmaceutical Design Kavalactone Pharmacophores for Major Cellular Drug Targets
Mini-Reviews in Medicinal Chemistry Development of Decision Tree Models for Substrates, Inhibitors, and Inducers of P-Glycoprotein
Current Drug Metabolism Proteomics in the Search for Biomarkers of Animal Cancer
Current Protein & Peptide Science Therapies of Hematological Malignancies: An Overview of the Potential Targets and Their Inhibitors
Current Chemical Biology Targeted Therapy for Advanced Urothelial Cancer of the Bladder: Where Do We Stand?
Anti-Cancer Agents in Medicinal Chemistry Anti-proliferative Properties of miR-20b and miR-363 from the miR-106a-363 Cluster on Human Carcinoma Cells
MicroRNA Fighting Tumor Cell Survival: Advances in the Design and Evaluation of Pim Inhibitors
Current Medicinal Chemistry Inhibition of Apoptosis in Pediatric Cancer by Survivin
Current Pediatric Reviews Synthesis and Biological Applications of Triazole Derivatives – A Review
Mini-Reviews in Organic Chemistry The Involvement of Post-Translational Modifications in Alzheimer's Disease
Current Alzheimer Research Insights into a Critical Role of the FOXO3a-FOXM1 Axis in DNA Damage Response and Genotoxic Drug Resistance
Current Drug Targets Therapeutic Transfer of DNA Encoding Adenoviral E1A
Recent Patents on Anti-Cancer Drug Discovery