The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Gene transfer into genomes of human cells by the sleeping beauty transposon system
Open accessAbstract
The 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.
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Cites
The sequence of the human genome
Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A., et al. (2001) · Science · doi:10.1126/science.1058040 · Cited by 13,909
Repeat-induced gene silencing in mammals
Garrick, D., Fiering, S., Martin, D. I. K., & Whitelaw, E. (1998) · Nature Genetics · doi:10.1038/ng0198-56 · Cited by 887 · cited 1×
“In contrast, random recombination of naked DNA often results in integration of concatamers, which have a propensity of being repressed over time [36,37].”
Background
Cited by
Tol2: a versatile gene transfer vector in vertebrates
Kawakami, K. (2007) · Genome Biology · doi:10.1186/gb-2007-8-s1-s7 · Cited by 566
Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse
Collier, L. S., Carlson, C. M., Ravimohan, S., Dupuy, A. J., & Largaespada, D. A. (2005) · Nature · doi:10.1038/nature03681 · Cited by 406
Self-citationCheon, D.-J., & Orsulic, S. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.3.121806.154244 · Cited by 395
Wu, S. C.-Y., Meir, Y.-J. J., Coates, C. J., Handler, A. M., Pelczar, P., Moisyadi, S., & Kaminski, J. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606979103 · Cited by 353
Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor
Jena, B., Dotti, G., & Cooper, L. J. N. (2010) · Blood · doi:10.1182/blood-2010-01-043737 · Cited by 297
Metadata
- Authors
- Geurts, A. M., Yang, Y., Clark, K. J., Liu, G., Cui, Z., Dupuy, A. J., Bell, J. B., Largaespada, D. A., & Hackett, P. B.
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2003-07
- Volume
- 8
- Issue
- 1
- Pages
- 108-117
- ISSN
- 1525-0016 (ISSN-L)
- OpenAlex
- W1993881548
- Cited by
- 351
- References
- 2
- FWCI
- 9.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Geurts, A. M., Yang, Y., Clark, K. J., Liu, G., Cui, Z., Dupuy, A. J., Bell, J. B., Largaespada, D. A., & Hackett, P. B. (2003). Gene transfer into genomes of human cells by the sleeping beauty transposon system. Molecular Therapy. https://doi.org/10.1016/s1525-0016(03)00099-6
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