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.
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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 |
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