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Chromosome Engineering with Lambda-Integrase Mediated Recombination System: The ACE System

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Mammalian Chromosome Engineering

Part of the book series: Methods in Molecular Biology ((MIMB,volume 738))

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Abstract

Mammalian satellite DNA-based artificial chromosomes (SATACs) are unique among the mammalian artificial chromosomes. These reproducibly generated de novo chromosomes are stably maintained in different species, readily purified from the host cell’s chromosomes and can be introduced into a variety of recipient cells. An artificial chromosome expression system (ACE system) has been developed on these SATACs to extend them for chromosome engineering. This system includes a Platform ACE containing multiple acceptor sites, specially designed targeting vector (ATV), and an ACE-integrase expression vector (pCXLamIntROK). Gene of interest are cloned into targeting vector (ATV), and site-specific loading of genes onto Platform ACE is facilitated by ACE-integrase mediated recombination. ACE system is suitable for multiple or subsequent loading of useful genes onto the same chromosome vector. This chapter describes the detailed procedure of chromosome engineering using the ACE system.

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References

  1. Carine, K., Solus, J., Waltzer, E., Manch-Citron, J., Hamkalo, B., and Scheffler, I. (1986) Chinese hamster cells with a minichromosome containing the centromere region of human chromosome 1. Somat. Cell Mol. Genet. 12, 479–491.

    Article  PubMed  CAS  Google Scholar 

  2. Harrington, J. J., Van Bokkelen, G., Mays, R. W., Gustashaw, K., and Willard, H. F. (1997) Formation of de novo centromeres and construction of first-generation human artificial microchromosomes. Nat. Genet. 15, 345–355.

    Article  PubMed  CAS  Google Scholar 

  3. Warburton, P. E., and Cooke, H. J. (1997) Hamster chromosomes containing amplified human alpha-satellite DNA show delayed sister chromatid separation in the absence of de novo kinetochore formation. Chromosoma 106, 145–159.

    Article  Google Scholar 

  4. Ikeno, M., Grimes, B., Okazaki, T., Nakano, M., Saitoh, K., Hoshino, H., et al. (1998) Construction of YAC-based mammalian artificial chromosomes. Nat. Biotech. 16, 431–439.

    Article  CAS  Google Scholar 

  5. Henning, K. A., Novotny, E. A., Compton, S. T., Guan, X. Y., Liu, P. P., and Ashlock, M. A. (1999) Human artificial chromosome generated by modification of a yeast artificial chromosome containing both human alpha satellite and single-copy sequences. Proc. Natl. Acad. Sci. USA 96, 592–597.

    Article  PubMed  CAS  Google Scholar 

  6. Ebersole, T. A., Ross, A., Clark, E., McGill, N., Schindelhauer, D., Cooke, H., and Grimes, B. (2000) Mammalian artificial chromosome formation from circular alphoid input DNA does not require telomere repeats. Hum. Mol. Genet. 9, 1623–1631.

    Article  PubMed  CAS  Google Scholar 

  7. Farr, C., Fantes, J., Goodfellow, P., and Cooke, H. (1991) Functional reintroduction of human telomeres into mammalian cells. Pro. Natl. Acad. Sci. USA 88, 7006–7010.

    Google Scholar 

  8. Farr, C. J., Stevanic, M., Thomson, E. J., Goodfellow, P. N., and Cooke, H. J. (1992) Telomere-associated chromosome fragmentation: applications in genome manipulation and analysis. Nat. Genet. 2, 275–282.

    Article  PubMed  CAS  Google Scholar 

  9. Farr, C. J., Bayne, R. A., Kipling, D., Mills, WW., Critcher, R., and Cooke, H. J. (1995) Generation of a human X-derived minichromosomeusing telomere-associated chromosome fragmentation. EMBO J. 14, 5444–5454.

    PubMed  CAS  Google Scholar 

  10. Heller, R., Brown, K. E., Burgtorf, C., and Brown, W. R. (1996) Minichromosomes derived from the human Y chromosome by telomere directed chromosome breakage. Proc. Natl. Acad. Sci. USA 93, 7125–7130.

    Article  PubMed  CAS  Google Scholar 

  11. Au, H. C., Mascarello, J. T., and Scheffler, I. E. (1999) Targeted integration of a dominant neoR marker into a 2- to 30-Mb human minichromosome and transfer between cells. Cytogenet. Cell Genet. 6, 1375–1382.

    Google Scholar 

  12. Sun, T. Q., Fernstermacher, D. A., and Vos, J. M. (1994) Human artificial episomal chromosomes for cloning large DNA fragments in human cells. Nat. Genet, 8, 33–41.

    Article  PubMed  CAS  Google Scholar 

  13. Kereső, J., Praznovszky, T., Cserpán, I., Fodor, K., Katona, R., Csonka, E., Fátyol, K., Holló, G., Szeles, A., and et al. (1996) De novo chromosome formations by large-scale amplification of the centromeric region of mouse chromosomes. Chromosome Res. 4, 226–239.

    Article  PubMed  Google Scholar 

  14. Praznovszky, T., Kereső, J., Tubak, V., Cserpán, I., Fátyol, K., and Hadlaczky, G. (1991) De novo chromosome formation in rodent cells. Proc. Natl. Acad. Sci. USA. 88, 11042–11046.

    Google Scholar 

  15. Csonka, E., Cserpán, I., Fodor, K., Hollo, G., Katona, R., Kereső, J., Praznovszky, T., Szakál, B., Telenius, A., de Jong, G., and et al. (2000) Novel generation of human satellite DNA-based artificial chromosomes in mammalian cells. J. Cell. Sci. 113, 3207–3216.

    PubMed  CAS  Google Scholar 

  16. Hadlaczky, G. (2001) Satellite DNA-based artificial chromosomes for use in gene therapy. Curr. Opin. Mol. Ther. 3, 125–132.

    PubMed  CAS  Google Scholar 

  17. Co, D. O., Borowski, A. H., Leung, J. D., van der Kaa, J., Hengst, S., Platenburg, G. J., et al. (2000) Generation of transgenic mice and germline transmission of a mammalian artificial chromosome introduced into embryos by pronuclear microinjection. Chrom. Res. 8, 183–191.

    Article  PubMed  CAS  Google Scholar 

  18. Lindenbaum, M., Perkins, E., Csonka, E., Fleming, E., Garcia, L., Greene, A., Gung, L., Hadlaczky, G., Lee, E., Leung, J., MacDonald, N.,Maxwell, A., Mills, K., Monteith, D., Perez, C. F., Shellard, J., Stewart, S., Stodola, T., Vadenborre, D., Vanderbyl, S., and Ledebur,Jr. H. C. (2004) A mammalian artificial chromosome engineering system (ACE System) applicable to biopharmaceutical protein production, transgenesis and gene-based cell therapy. Nucleic Acids Res. 32, e172.

    Article  PubMed  Google Scholar 

  19. Pinkel, D., Straume, T., and Gray, J. W. (1986) Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. Proc. Natl. Acad. Sci. USA 83, 2937–2938.

    Article  Google Scholar 

  20. Kennard, M. L., Goosney, D. L., Monteith, D., Roe, S., Fischer, D., Mott, J. (2009) Auditioning of CHO host cell lines using the artificial chromosome expression (ACE) technology. Biotechnol. Bioeng. 104, 526–539.

    Article  PubMed  CAS  Google Scholar 

  21. Kennard, M. L., Goosney, D. L., Monteith, D., Zhang, L., Moffat, M., Fischer, D., Mott, J. (2009) The generation of stable, high MAb expressioning CHO cell lines based on the artificial chromosome expression (ACE) technology. Biotechnol. Bioeng. 104, 540–553.

    Article  PubMed  CAS  Google Scholar 

  22. Katona, R. L., Sinkó, I., Holló, G., Székely Szűcs, K., Praznovszky, T., Kereső, J., Csonka, E., Fodor, K., Cserpán, I., Szakál, B., Blazsó, P.,Udvardy, A., and Hadlaczky, G. (2008) A combined artificial chromosome-stem cell therapy method in a model experiment aimed at the treatment of Krabbe’s disease in the Twitcher mouse. Cell. Mol. Life Sci. 65, 3830–3838.

    Article  PubMed  CAS  Google Scholar 

  23. Vanderbyl, S., MacDonald, G. N., Sidhu, S., Gung, I., Telenius, A., Perez, C., and Perkins, E. (2004) Transfer and stable transgene expression of a mammalian artificial chromosome into bone marrow-derived human mesenchymal stem cells. Stem Cells. 22, 324–333.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary

    Tünde Praznovszky

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  1. Tünde Praznovszky
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Correspondence to Tünde Praznovszky .

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Editors and Affiliations

  1. Biological Research Center, Institute of Genetics, Hungarian Academy of Sciences, Temesvári körút 62, Szeged, 6723, Hungary

    Gyula Hadlaczky

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Praznovszky, T. (2011). Chromosome Engineering with Lambda-Integrase Mediated Recombination System: The ACE System. In: Hadlaczky, G. (eds) Mammalian Chromosome Engineering. Methods in Molecular Biology, vol 738. Humana Press. https://doi.org/10.1007/978-1-61779-099-7_10

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  • DOI: https://doi.org/10.1007/978-1-61779-099-7_10

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-098-0

  • Online ISBN: 978-1-61779-099-7

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