The φC31 integrase system for gene therapy

被引:105
作者
Calos, Michele P. [1 ]
机构
[1] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA
关键词
att site; genetic disease; genomic integration; liver; non-viral; phage; serine recombinase; site-specific;
D O I
10.2174/156652306779010642
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The phi C31 integrase system represents a novel technology that opens up new possibilities for gene therapy. The phi C31 integrase can integrate introduced plasmid DNA into preferred locations in unmodified mammalian genomes, resulting in robust, long-term expression of the integrated transgene. This review describes the nature of the integration reaction and the genomic integration sites used by the enzyme in human cells. Preclinical applications of the system to gene therapy to date are summarized, including in vivo use in liver, muscle, eye, and joint and ex vivo use in skin keratinocytes, muscle precursor cells, and T cell lines. The safety of this phage integrase system for gene therapy is evaluated, and its strengths and limitations are compared to other gene therapy approaches. Ongoing and planned improvements to the phage integrase system are discussed. We conclude that gene therapy strategies using phi C31 integrase and its derivatives offer great promise for success in the near term.
引用
收藏
页码:633 / 645
页数:13
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