期刊
MOLECULAR THERAPY
卷 19, 期 9, 页码 1591-1601出版社
CELL PRESS
DOI: 10.1038/mt.2011.136
关键词
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资金
- JST
- CREST
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- New Energy and Industrial Technology Development Organization (NEDO) from the Ministry of Economy, Trade and Industry of Japan
- Grants-in-Aid for Scientific Research [21249022] Funding Source: KAKEN
Random integration of conventional gene delivery vectors such as viruses, plasmids, P1 phage-derived artificial chromosomes, bacterial artificial chromosomes and yeast artificial chromosomes can be associated with transgene silencing. Furthermore, integrated viral sequences can activate oncogenes adjacent to the insertion site resulting in cancer. Various human artificial chromosomes (HACs) exhibit several potential characteristics desired for an ideal gene delivery vector, including stable episomal maintenance and the capacity to carry large genomic loci with their regulatory elements, thus allowing the physiological regulation of the introduced gene in a manner similar to that of native chromosomes. HACs have been generated mainly using either a top-down approach (engineered chromosomes), or a bottom-up approach (de novo artificial chromosomes). The recent emergence of stem cell-based tissue engineering has opened up new avenues for gene and cell therapies. This review describes the lessons learned and prospects identified mainly from studies in the construction of HACs and HAC-mediated gene expression systems in cultured cells, as well as in animals.
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