| RRC ID |
1506
|
| 著者 |
Kakeda M, Hiratsuka M, Nagata K, Kuroiwa Y, Kakitani M, Katoh M, Oshimura M, Tomizuka K.
|
| タイトル |
Human artificial chromosome (HAC) vector provides long-term therapeutic transgene expression in normal human primary fibroblasts.
|
| ジャーナル |
Gene Ther
|
| Abstract |
Human artificial chromosomes (HACs) segregating freely from host chromosomes are potentially useful to ensure both safety and duration of gene expression in therapeutic gene delivery. However, low transfer efficiency of intact HACs to the cells has hampered the studies using normal human primary cells, the major targets for ex vivo gene therapy. To elucidate the potential of HACs to be vectors for gene therapy, we studied the introduction of the HAC vector, which is reduced in size and devoid of most expressed genes, into normal primary human fibroblasts (hPFs) with microcell-mediated chromosome transfer (MMCT). We demonstrated the generation of cytogenetically normal hPFs harboring the structurally defined and extra HAC vector. This introduced HAC vector was retained stably in hPFs without translocation of the HAC on host chromosomes. We also achieved the long-term production of human erythropoietin for at least 12 weeks in them. These results revealed the ability of HACs as novel options to circumvent issues of conventional vectors for gene therapy.
|
| 巻・号 |
12(10)
|
| ページ |
852-6
|
| 公開日 |
2005-5-1
|
| DOI |
10.1038/sj.gt.3302483
|
| PII |
3302483
|
| PMID |
15750614
|
| MeSH |
Cells, Cultured
Chromosomes, Artificial, Human*
Erythropoietin / genetics*
Erythropoietin / metabolism
Fibroblasts / metabolism*
Gene Expression
Genetic Therapy / methods*
Genetic Vectors / administration & dosage*
Genetic Vectors / genetics
Humans
Time Factors
Transduction, Genetic / methods*
Transgenes
|
| IF |
4.128
|
| 引用数 |
50
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
GENETICS & HEREDITY
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HFL-I(RCB0521)
HUC-F2(RCB0436)
HF19(RCB0210) |
