RRC ID |
44225
|
著者 |
Yakura Y, Ishihara C, Kurosaki H, Kazuki Y, Komatsu N, Okada Y, Doi T, Takeya H, Oshimura M.
|
タイトル |
An induced pluripotent stem cell-mediated and integration-free factor VIII expression system.
|
ジャーナル |
Biochem Biophys Res Commun
|
Abstract |
Human artificial chromosome (HAC) has several advantages as a gene therapy vector, including stable episomal maintenance and the ability to carry large gene inserts. Induced pluripotent stem (iPS) cells also have a great potential for gene therapy, which can be generated from an individual's own tissues and contribute to any tissues when reintroduced. A Sendai virus (SeV) vector with reprogramming factors is a powerful tool for generating iPS cells because of the high infection efficiency without the risk of integration into host chromosomes. In this study, we developed an iPS cell-mediated and integration-free coagulation factor VIII (FVIII) expression system using non-integrating SeV- and HAC-vectors. Multiple human FVIII genes, which were under the control of the megakaryocyte-specific platelet factor-4 (PF4) promoter for development of a treatment for hemophilia A, were inserted into a HAC vector (PF4-FVIII-HAC). The PF4-FVIII-HAC was introduced into SeV vector-mediated iPS cells derived from a mouse model of hemophilia A. After in vitro differentiation of iPS cells with the PF4-FVIII-HAC into megakaryocytes/platelets, the PF4-FVIII-HAC resulted in expression of FVIII. This study has developed the iPS cell-mediated PF4-driven FVIII expression system using two non-integrating vectors; therefore, this system may be a promising tool for safer gene- and cell-therapy of hemophilia A.
|
巻・号 |
431(2)
|
ページ |
336-41
|
公開日 |
2013-2-8
|
DOI |
10.1016/j.bbrc.2012.12.096
|
PII |
S0006-291X(12)02456-4
|
PMID |
23291180
|
MeSH |
Animals
Cell Differentiation
Cell Line, Tumor
Chromosomes, Artificial, Human / genetics*
Disease Models, Animal
Factor VIII / genetics*
Genetic Therapy / methods*
Genetic Vectors / genetics
Hemophilia A / therapy*
Humans
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / metabolism*
Induced Pluripotent Stem Cells / transplantation*
Mice
Platelet Factor 4 / genetics
Platelet Factor 4 / metabolism
Promoter Regions, Genetic
Sendai virus
|
IF |
2.985
|
引用数 |
17
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
OP9(RCB1124) |