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Gene transfer into genomes of human cells by the sleeping beauty transposon system
Aron M. Geurts; Ying Yang; Karl J. Clark; Geyi Liu; Zongbin Cui; Adam J. Dupuy; Jason B. Bell; David A. Largaespada; Perry B. Hackett; Geurts, AM, Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA
2003
Source PublicationMOLECULAR THERAPY
Volume8Issue:1Pages:108-117
AbstractThe Sleeping Beauty (SB) transposon system, derived from teleost fish sequences, is extremely effective at delivering DNA to vertebrate genomes, including those of humans. We have examined several parameters of the SB system to improve it as a potential, nonviral vector for gene therapy. Our investigation centered on three features: the carrying capacity of the transposon for efficient integration into chromosomes of HeLa cells, the effects of overexpression of the SB transposase gene on transposition rates, and improvements in the activity of SB transposase to increase insertion rates of transgenes into cellular chromosomes. We found that SB transposons of about 6 kb retained 50% of the maximal efficiency of transposition, which is sufficient to deliver 70-80% of identified human cDNAs with appropriate transcriptional regulatory sequences. Overexpression inhibition studies revealed that there are optimal ratios of SB transposase to transposon for maximal rates of transposition, suggesting that conditions of delivery of the two-part transposon system are important for the best gene-transfer efficiencies. We further refined the SB transposase to incorporate several amino acid substitutions, the result of which led to an improved transposase called SB11. With SB11 we are able to achieve transposition rates that are about 100-fold above those achieved with plasmids that insert into chromosomes by random recombination. With the recently described improvements to the transposon itself, the SB system appears to be a potential gene-transfer tool for human gene therapy.
KeywordGene Therapy Inverted Terminal Repeats Site-specific Mutagenesis Transposase
DepartmentUniv Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA; Univ Minnesota, Arnold & Mabel Beckman Ctr Transposon Res, Minneapolis, MN 55455 USA; Discovery Genom Inc, Minneapolis, MN 55413 USA; Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China
Subject AreaResearch & Experimental ; Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine
Indexed BySCI
WOS IDWOS:000184066900017
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Cited Times:250[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/152342/9684
Collection期刊论文
Corresponding AuthorGeurts, AM, Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA
Recommended Citation
GB/T 7714
Aron M. Geurts,Ying Yang,Karl J. Clark,et al. Gene transfer into genomes of human cells by the sleeping beauty transposon system[J]. MOLECULAR THERAPY,2003,8(1):108-117.
APA Aron M. Geurts.,Ying Yang.,Karl J. Clark.,Geyi Liu.,Zongbin Cui.,...&Geurts, AM, Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.(2003).Gene transfer into genomes of human cells by the sleeping beauty transposon system.MOLECULAR THERAPY,8(1),108-117.
MLA Aron M. Geurts,et al."Gene transfer into genomes of human cells by the sleeping beauty transposon system".MOLECULAR THERAPY 8.1(2003):108-117.
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