A combined artificial chromosome-stem cell therapy method in a model experiment aimed at the treatment of Krabbe's disease in the Twitcher mouse

被引：7

作者：

Katona, R. L. ^{[1
]}

Sinko, I. ^{[1
]}

Hollo, G. ^{[1
]}

Szuecs, K. Szekely ^{[1
]}

Praznovszky, T. ^{[1
]}

Keresoe, J. ^{[1
]}

Csonka, E. ^{[1
]}

Fodor, K. ^{[1
]}

Cserpan, I. ^{[1
]}

Szakal, B. ^{[1
]}

Blazso, P. ^{[1
]}

Udvardy, A. ^{[2
]}

Hadlaczky, G. ^{[1
]}

机构：

[1] Hungarian Acad Sci, Inst Genet, Biol Res Ctr, H-6726 Szeged, Hungary

[2] Hungarian Acad Sci, Inst Biochem, Biol Res Ctr, H-6726 Szeged, Hungary

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2008年 / 65卷 / 23期

关键词：

Mammalian artificial chromosome; stem cell; Krabbe's disease; transgenic mouse; gene therapy;

D O I：

10.1007/s00018-008-8442-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mammalian artificial chromosomes (MACs) are safe, stable, non-integrating genetic vectors with almost unlimited therapeutic transgene-carrying capacity. The combination of MAC and stem cell technologies offers a new strategy for stem cell-based therapy, the efficacy of which was confirmed and validated by using a mouse model of a devastating monogenic disease, galactocerebrosidase deficiency (Krabbe's disease). Therapeutic MACs were generated by sequence-specific loading of galactocerebrosidase transgenes into a platform MAC, and stable, pluripotent mouse embryonic stem cell lines were established with these chromosomes. The transgenic stem cells were thoroughly characterized and used to produce chimeric mice on the mutant genetic background. The lifespan of these chimeras was increased twofold, verifying the feasibility of the development of MAC-stem cell systems for the delivery of therapeutic genes in stem cells to treat genetic diseases and cancers, and to produce cell types for cell replacement therapies.

引用

页码：3830 / 3838

页数：9

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