Site-specific transfer of an intact β-globin gene cluster through a new targeting vector

The ideal gene-therapy vector for treating genetic disorders should deliver intact therapeutic genes and their essential regulatory elements into the specific “safe genomic site” and realize long-term, self-regulatory expression. For β-thalassemia gene therapy, viral vectors have been broadly used,...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2007-04, Vol.356 (1), p.32-37
Main Authors: Zhou, Hai-sheng, Zhao, Na, Li, Lei, Dong, Wen-ji, Wu, Xue-song, Hao, De-long, Guo, Zhi-chen, Xia, Kun, Xia, Jia-hui, Liu, De-pei, Liang, Chih-chuan
Format: Article
Language:English
Subjects:
Binding Sites
Blotting, Southern
Gene Expression
Gene Targeting - methods
Genetic Vectors - genetics
Globins - genetics
Homologous recombination
Human chromosome-derived vector
Human β-globin gene cluster
Humans
In Situ Hybridization, Fluorescence - methods
K562 Cells
Multigene Family
Recombination, Genetic
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
Site-specific integration
Transfection - methods
β-Thalassemia
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Summary:The ideal gene-therapy vector for treating genetic disorders should deliver intact therapeutic genes and their essential regulatory elements into the specific “safe genomic site” and realize long-term, self-regulatory expression. For β-thalassemia gene therapy, viral vectors have been broadly used, but the accompanying insertional mutation and immunogenicity remain problematic. Hence, we aimed to develop new non-viral vectors that are efficient and safe in treating diseases. As previous studies have demonstrated that physiological expression of β-globin genes requires both a 5′ locus control region and 3′ specific elements, we constructed a new human chromosome-derived targeting vector to transfer the intact β-globin gene cluster into K562 cells. The whole β-globin gene cluster was precisely integrated into the target site and expressed in a self-regulatory pattern. The results proved that the human chromosome-derived vector was specifically targeted to the human genome and this could provide a novel platform for further gene therapy research.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2007.02.074