| RRC ID |
37659
|
| 著者 |
Kazuki Y, Hiratsuka M, Takiguchi M, Osaki M, Kajitani N, Hoshiya H, Hiramatsu K, Yoshino T, Kazuki K, Ishihara C, Takehara S, Higaki K, Nakagawa M, Takahashi K, Yamanaka S, Oshimura M.
|
| タイトル |
Complete genetic correction of ips cells from Duchenne muscular dystrophy.
|
| ジャーナル |
Mol Ther
|
| Abstract |
Human artificial chromosome (HAC) has several advantages as a gene therapy vector, including stable episomal maintenance that avoids insertional mutations and the ability to carry large gene inserts including the regulatory elements. Induced pluripotent stem (iPS) cells have great potential for gene therapy, as such cells can be generated from the individual's own tissues, and when reintroduced can contribute to the specialized function of any tissue. As a proof of concept, we show herein the complete correction of a genetic deficiency in iPS cells derived from Duchenne muscular dystrophy (DMD) model (mdx) mice and a human DMD patient using a HAC with a complete genomic dystrophin sequence (DYS-HAC). Deletion or mutation of dystrophin in iPS cells was corrected by transferring the DYS-HAC via microcell-mediated chromosome transfer (MMCT). DMD patient- and mdx-specific iPS cells with the DYS-HAC gave rise to differentiation of three germ layers in the teratoma, and human dystrophin expression was detected in muscle-like tissues. Furthermore, chimeric mice from mdx-iPS (DYS-HAC) cells were produced and DYS-HAC was detected in all tissues examined, with tissue-specific expression of dystrophin. Therefore, the combination of patient-specific iPS cells and HAC-containing defective genes represents a powerful tool for gene and cell therapies.
|
| 巻・号 |
18(2)
|
| ページ |
386-93
|
| 公開日 |
2010-2-1
|
| DOI |
10.1038/mt.2009.274
|
| PII |
S1525-0016(16)31621-5
|
| PMID |
19997091
|
| PMC |
PMC2839293
|
| MeSH |
Animals
CHO Cells
Cell Line
Cells, Cultured
Chromosomes, Artificial, Human / genetics
Cricetinae
Cricetulus
Dystrophin / genetics
Humans
Immunohistochemistry
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / metabolism
Induced Pluripotent Stem Cells / physiology*
Mice
Mice, Inbred mdx
Models, Theoretical
Muscular Dystrophy, Duchenne / therapy*
Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
|
| IF |
8.986
|
| 引用数 |
174
|
|
WOS 分野
|
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
MEDICINE, RESEARCH & EXPERIMENTAL
GENETICS & HEREDITY
|
| リソース情報 |
| ヒト・動物細胞 |
iPS-MEF-Ng-20D-17(APS0001) |
