Progress and prospects: oligonucleotide-directed gene modification in mouse embryonic stem cells: a route to therapeutic application

被引:43
作者
Aarts, M. [1 ]
Riele, H. Te [1 ]
机构
[1] Netherlands Canc Inst, Div Mol Biol, NL-1066 CX Amsterdam, Netherlands
关键词
subtle gene modification; oligonucleotides; embryonic stem cells; DNA mismatch repair; SINGLE-STRANDED OLIGONUCLEOTIDES; DNA MISMATCH-REPAIR; CHIMERIC RNA/DNA OLIGONUCLEOTIDES; MAMMALIAN-CELLS; HOMOLOGOUS RECOMBINATION; ES CELLS; IN-VIVO; METHYLATION TOLERANCE; NUCLEOTIDE EXCHANGE; SEQUENCE CORRECTION;
D O I
10.1038/gt.2010.161
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
Gene targeting by single-stranded oligodeoxyribonucleotides (ssODNs) is a promising technique for introducing site-specific sequence alterations without affecting the genomic organization of the target locus. Here, we discuss the significant progress that has been made over the last 5 years in unraveling the mechanisms and reaction parameters underlying ssODN-mediated gene targeting. We will specifically focus on ssODN-mediated gene targeting in murine embryonic stem cells (ESCs) and the impact of the DNA mismatch repair (MMR) system on the targeting process. Implications of novel findings for routine application of ssODN-mediated gene targeting and challenges that need to be overcome for future therapeutic applications are highlighted. Gene Therapy (2011) 18, 213-219; doi:10.1038/gt.2010.161; published online 16 December 2010
引用
收藏
页码:213 / 219
页数:7
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