Strategies for the episomal modification of cells

Current Opinion in Molecular Therapeutics

Volumn 11, Issue 4, 2009, Pages 433-441

  Wong, Suet Ping ^a   Argyros, Orestis ^a   Coutelle, Charles ^a   Harbottle, Richard P ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Cell modification; Episomal non viral vector; Gene expression; Gene therapy; Integrating non viral vector; Replication deficient virus; Scaffold matrix attachment region

Indexed keywords

ADENOVIRUS VECTOR; DNA; LENTIVIRUS VECTOR; PARVOVIRUS VECTOR; PLASMID VECTOR;

CARCINOGENESIS; CELL DIVISION; CHROMOSOME; DNA MODIFICATION; DNA VECTOR; EPISOME; EPSTEIN BARR VIRUS; GENE LOCUS; GENE THERAPY; GENE VECTOR; GENOME; GENOTOXICITY; HERPES SIMPLEX VIRUS; HUMAN; MATRIX ATTACHMENT REGION; NONHUMAN; REVIEW; RISK ASSESSMENT; TRANSGENE; YEAST;

ANIMALS; CELLS; DNA REPLICATION; GENETIC VECTORS; HUMANS; MATRIX ATTACHMENT REGIONS; PLASMIDS;

MUS;

EID: 68649119307     PISSN: 14648431     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (119)

1. Ellerman V, Bang O: Experimentelle leukamie bei Huhnern. Zentralbl Bakteriol Parasitenkd Infectionskr Hyg Abt Orig (1908) 46:595-609.
2. Rous P: A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J Exp Med (1911) 13(4):397-411.
3. Maeda N, Fan H, Yoshikai Y: Oncogenesis by retroviruses: Old and new paradigms. Rev Med Virol (2008) 18(6):387-405.
4. Aiuti A, Slavin S, Aker M, Ficara F, Deola S, Mortellaro A, Morecki S, Andolfi G, Tabucchi A, Carlucci F, Marinello E et al: Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science (2002) 296 (5577): 2410-2413.
5. Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, Gross F, Yvon E, Nusbaum P, Selz F, Hue C, Certain S, Casanova JL, Bousso P et al: Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science (2000) 288 (5466):669-672.
6. Gaspar HB, Parsley KL, Howe S, King D, Gilmour KC, Sinclair J, Brouns G, Schmidt M, Von Kalle C, Barington T, Jakobsen MA et al: Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped γ retroviral vector. Lancet (2004) 364 (9452):2181-2187.
7. Hacein-Bey-Abina S, Le Deist F, Carlier F, Bouneaud C, Hue C, De Villartay JP, Thrasher AJ, Wulffraat N, Sorensen R, Dupuis-Girod S, Fischer A et al: Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med (2002) 346(16):1185-1193.
8. Hacein-Bey-Abina S, Garrigue A, Wang GP, Soulier J, Lim A, Morillon E, Clappier E, Caccavelli L, Delabesse E, Beldjord K, Asnafi V et al: Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest (2008) 118(9):3132-3142.
9. An in-depth analysis of the proto-oncogenes activated following retroviral-mediated insertional mutagenesis. This study further highlights the necessity for safe episomal vectors for clinical application.
10. Howe SJ, Mansour MR, Schwarzwaelder K, Bartholomae C, Hubank M, Kempski H, Brugman MH, Pike-Overzet K, Chatters SJ, de Ridder D, Gilmour KC et al: Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest (2008) 118(9):3143-3150.
11. Hacein-Bey-Abina S, von Kalle C, Schmidt M, Le Deist F, Wulffraat N, McIntyre E, Radford I, Villeval JL, Fraser CC, Cavazzana-Calvo M, Fischer A: A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med (2003) 348(3):255-256.
12. Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, Lim A, Osborne CS, Pawliuk R, Morillon E, Sorensen R et al: LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science (2003) 302 (5644):415-419.
13. Lechardeur D, Lukacs GL: Nucleocytoplasmic transport of plasmid DNA: A perilous journey from the cytoplasm to the nucleus. Hum Gene Ther (2006) 17(9):882-889.
14. Vigdal TJ, Kaufman CD, Izsvák Z, Voytas DF, Ivics Z: Common physical properties of DNA affecting target site selection of sleeping beauty and other Tc1/mariner transposable elements. J Mol Biol (2002) 323(3):441-452.
15. Geurts AM, Yang Y, Clark KJ, Liu G, Cui Z, Dupuy AJ, Bell JB, Largaespada DA, Hackett PB: Gene transfer into genomes of human cells by the sleeping beauty transposon system. Mol Ther (2003) 8(1):108-117.
16. Karsi A, Moav B, Hackett P, Liu Z: Effects of insert size on transposition efficiency of the sleeping beauty transposon in mouse cells. Mar. Biotechnol (2001) 3(3):241-245.
17. Andreas S, Schwenk F, Kuter-Luks B, Faust N, Kuhn R: Enhanced efficiency through nuclear localization signal fusion on phage φC31-integrase: Activity comparison with Cre and FLPe recombinase in mammalian cells. Nucleic Acids Res (2002) 30(11):2299-2306.
18. Liu J, Jeppesen I, Nielsen K, Jensen TG: φc31 integrase induces chromosomal aberrations in primary human fibroblasts. Gene Ther (2006) 13(15):1188-1190.
19. Ehrhardt A, Engler JA, Xu H, Cherry AM, Kay MA: Molecular analysis of chromosomal rearrangements in mammalian cells after φC31-mediated integration. Hum Gene Ther (2006) 17(11):1077-1094.
20. Yang Y, Nunes FA, Berencsi K, Furth EE, Gonczol E, Wilson JM: Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy. Proc Natl Acad Sci USA (1994) 91(10):4407-4411.
21. Danthinne X, Imperiale MJ: Production of first generation adenovirus vectors: A review. Gene Ther (2000) 7(20):1707-1714.
22. Kochanek S, Schiedner G, Volpers C: High-capacity 'gutless' adenoviral vectors. Curr Opin Mol Ther (2001) 3(5):454-463.
23. Morral N, O'Neal W, Rice K, Leland M, Kaplan J, Piedra PA, Zhou H, Parks RJ, Velji R, Aguilar-Córdova E, Wadsworth S et al: Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons. Proc Natl Acad Sci USA (1999) 96(22):12816-12821.
24. Toietta G, Mane VP, Norona WS, Finegold MJ, Ng P, McDonagh AF, Beaudet AL, Lee B: Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector. Proc Natl Acad Sci USA (2005) 102(11):3930-3935.
25. Brunetti-Pierri N, Stapleton GE, Palmer DJ, Zuo Y, Mane VP, Finegold MJ, Beaudet AL, Leland MM, Mullins CE, Ng P: Pseudohydrodynamic delivery of helper-dependent adenoviral vectors into non-human primates for liver-directed gene therapy. Mol Ther (2007) 15(4):732-740.
26. Ehrhardt A, Kay MA: A new adenoviral helper-dependent vector results in long-term therapeutic levels of human coagulation Factor IX at low doses in vivo. Blood (2002) 99(11):3923-3930.
27. Buch PK, Bainbridge JW, Ali RR: AAV-mediated gene therapy for retinal disorders: From mouse to man. Gene Ther (2008) 15(11):849-857.
28. Thorough review of the generation of AAV vectors, focusing on their prospects and application in clinical trials for retinal disease.
29. Moss RB, Milla C, Colombo J, Accurso F, Zeitlin PL, Clancy JP, Spencer LT, Pilewski J, Waltz DA, Dorkin HL, Ferkol T et al: Repeated aerosolized AAV-CFTR for treatment of cystic fibrosis: A randomized placebo-controlled phase 2B trial. Hum Gene Ther (2007) 18(8):726-732.
30. Hasbrouck NC, High KA: AAV-mediated gene transfer for the treatment of hemophilia B: Problems and prospects. Gene Ther (2008) 15(11):870-875.
31. Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, Bland RJ, Young D, Strybing K, Eidelberg D, During MJ: Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: An open label, phase I trial. Lancet (2007) 369 (9579):2097-2105.
32. Nakai H, Montini E, Fuess S, Storm TA, Grompe M, Kay MA: AAV serotype 2 vectors preferentially integrate into active genes in mice. Nat Genet (2003) 34(3):297-302.
33. Donsante A, Miller DG, Li Y, Vogler C, Brunt EM, Russell DW, Sands MS: AAV vector integration sites in mouse hepatocellular carcinoma. Science (2007) 317 (5837):477.
34. Berges BK, Wolfe JH, Fraser NW: Transduction of brain by herpes simplex virus vectors. Mol Ther (2007) 15(1):20-29.
35. Wolfe D, Goins WF, Yamada M, Moriuchi S, Krisky DM, Oligino TJ, Marconi PC, Fink DJ, Glorioso JC: Engineering herpes simplex virus vectors for CNS applications. Exp Neurol (1999) 159(1):34-46.
36. Goss JR, Gold MS, Glorioso JC: HSV vector-mediated modification of primary nociceptor afferents: An approach to inhibit chronic pain. Gene Ther (2009) 16(4):493-501.
37. Craft AM, Krisky DM, Wechuck JB, Lobenhofer EK, Jiang Y, Wolfe DP, Glorioso JC: Herpes simplex virus-mediated expression of Pax3 and MyoD in embryoid bodies results in lineage-related alterations in gene expression profiles. Stem Cells (2008) 26(12):3119-3129.
38. Alba R, Bosch A, Chillon M: Gutless adenovirus: Last-generation adenovirus for gene therapy. Gene Ther (2005) 12 (Suppl 1) :S18-S27.
39. Palmer D, Ng P: Improved system for helper-dependent adenoviral vector production. Mol Ther (2003) 8(5):846-852.
40. Sakhuja K, Reddy PS, Ganesh S, Cantaniag F, Pattison S, Limbach P, Kayda DB, Kadan MJ, Kaleko M, Connelly S: Optimization of the generation and propagation of gutless adenoviral vectors. Hum Gene Ther (2003) 14(3):243-254.
41. Naldini L, Blömer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, Trono D: In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. bScience (1996) 272 (5259):263-267.
42. Rahim AA, Wong AM, Howe SJ, Buckley SM, Acosta-Saltos AD, Elston KE, Ward NJ, Philpott NJ, Cooper JD, Anderson PN, Waddington SN et al: Efficient gene delivery to the adult and fetalCNS using pseudotyped non-integrating lentiviral vectors. Gene Ther (2009) 16(4):509-520.
43. Yáñez-Muñoz RJ, Balaggan KS, MacNeil A, Howe SJ, Schmidt M, Smith AJ, Buch P, MacLaren RE, Anderson PN, Barker SE, Duran Y et al: Effective gene therapy with nonintegrating lentiviral vectors. Nat Med (2006) 12(3):348-353.
44. Integration deficient lentiviruses efficiently sustain transgene expression in brain and ocular tissues, and successfully rescue rodent models of retinal degeneration.
45. Stevenson M, Haggerty S, Lamonica CA, Meier CM, Welch SK, Wasiak AJ: Integration is not necessary for expression of human immunodeficiency virus type 1 protein products. J Virol (1990) 64(5):2421-2425.
46. Philippe S, Sarkis C, Barkats M, Mammeri H, Ladroue C, Petit C, Mallet J, Serguera C: Lentiviral vectors with a defective integrase allow efficient and sustained transgene expression in vitro and in vivo. Proc Natl Acad Sci USA (2006) 103(47):17684-17689.
47. Yates JL, Warren N, Sugden B: Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. Nature (1985) 313 (6005):812-815.
48. Reisman D, Yates J, Sugden B: A putative origin of replication of plasmids derived from Epstein-Barr virus is composed of two cis-acting components. Mol Cell Biol (1985) 5(8):1822-1832.
49. Myers RM, Tjian R: Construction and analysis of simian virus 40 origins defective in tumor antigen binding and DNA replication. Proc Natl Acad Sci USA (1980) 77(11):6491-6495.
50. Lupton S, Levine AJ: Mapping genetic elements of Epstein-Barr virus that facilitate extrachromosomal persistence of Epstein-Barr virus-derived plasmids in human cells. Mol Cell Biol (1985) 5(10):2533-2542.
51. Middleton T, Sugden B: Retention of plasmid DNA in mammalian cells is enhanced by binding of the Epstein-Barr virus replication protein EBNA1. J Virol (1994) 68(6):4067-4071.
52. Strayer DS: Gene therapy using SV40-derived vectors: What does the future hold? J Cell Physiol (1999) 181(3):375-384.
53. Strayer D, Branco F, Zern MA, Yam P, Calarota SA, Nichols CN, Zaia JA, Rossi J, Li H, Parashar B, Ghosh S et al: Durability of transgene expression and vector integration: Recombinant SV40-derived gene therapy vectors. Mol Ther (2002) 6(2):227-237.
54. Conese M, Auriche C, Ascenzioni F: Gene therapy progress and prospects: Episomally maintained self-replicating systems. Gene Ther (2004) 11(24):1735-1741.
55. Kotzamanis G, Abdulrazzak H, Gifford-Garner J, Haussecker PL, Cheung W, Grillot-Courvalin C, Harris A, Kittas C, Kotsinas A, Gorgoulis V, Huxley C: CFTR expression from a BAC carrying the complete human gene and associated regulatory elements. J Cell Mol Med (2008) :doi:10.1111/j.1582-4934.
56. Simpson K, McGuigan A, Huxley C: Stable episomal maintenance of yeast artificial chromosomes in human cells. Mol Cell Biol (1996) 16(9):5117-5126.
57. Murray AW, Szostak JW: Construction of artificial chromosomes in yeast. Nature (1983) 305 (5931):189-193.
58. Harrington JJ, Van Bokkelen G, Mays RW, Gustashaw K, Willard HF: Formation of de novo centromeres and construction of firstgeneration human artificial microchromosomes. Nat Genet (1997) 15(4):345-355.
59. Basu J, Willard HF: Artificial and engineered chromosomes: Non-integrating vectors for gene therapy. Trends Mol Med (2005) 11(5):251-258.
60. Farr CJ, Stevanovic M, Thomson EJ, Goodfellow PN, Cooke HJ: Telomere-associated chromosome fragmentation: Applications in genome manipulation and analysis. Nat Genet (1992) 2(4):275-282.
61. Lipps HJ, Jenke AC, Nehlsen K, Scinteie MF, Stehle IM, Bode J: Chromosome-based vectors for gene therapy. Gene (2003) 304:23-33.
62. Glover DJ, Lipps HJ, Jans DA: Towards safe, non-viral therapeutic gene expression in humans. Nat Rev Genet (2005) 6(4):299-310.
63. Ebersole TA, Ross A, Clark E, McGill N, Schindelhauer D, Cooke H, Grimes B: Mammalian artificial chromosome formation from circular alphoid input DNA does not require telomere repeats. Hum Mol Genet (2000) 9(11):1623-1631.
64. Jackson DA, Juranek S, Lipps HJ: Designing nonviral vectors for efficient gene transfer and long-term gene expression. Mol Ther (2006) 14(5):613-626.
65. Suzuki N, Nishii K, Okazaki T, Ikeno M: Human artificial chromosomes constructed using the bottom-up strategy are stably maintained in mitosis and efficiently transmissible to progeny mice. J Biol Chem (2006) 281(36):26615-26623.
66. Hoshiya H, Kazuki Y, Abe S, Takiguchi M, Kajitani N, Watanabe Y, Yoshino T, Shirayoshi Y, Higaki K, Messina G, Cossu G et al: A highly stable and nonintegrated human artificial chromosome (HAC) containing the 2.4 Mb entire human dystrophin gene. Mol Ther (2009) 17(2):309-317.
67. A HAC capable of stable, tissue-specific expression of the complete dystrophin gene in chimeric mice has major implications for future Duchenne muscular dystrophy therapies.
68. Paulis M, Bensi M, Orioli D, Mondello C, Mazzini G, D'Incalci M, Falcioni C, Radaelli E, Erba E, Raimondi E, De Carli L: Transfer of a human chromosomal vector from a hamster cell line to a mouse embryonic stem cell line. Stem Cells (2007) 25(10): 2543-2550.
69. Carlson SR, Rudgers GW, Zieler H, Mach JM, Luo S, Grunden E, Krol C, Copenhaver GP, Preuss D: Meiotic transmission of an in vitro - assembled autonomous maize minichromosome. PLoS Genet (2007) 3(10):1965-1974.
70. Moralli D, Simpson KM, Wade-Martins R, Monaco ZL: A novel human artificial chromosome gene expression system using herpes simplex virus type 1 vectors. EMBO Rep (2006) 7(9): 911-918.
71. Lufino MM, Manservigi R, Wade-Martins R: An S/MAR-based infectious episomal genomic DNA expression vector provides long-term regulated functional complementation of LDLR deficiency. Nucleic Acids Res (2007) 35(15) :e98.
72. The generation of an artificial chromosome containing a genomic locus capable of restoring LDLR function to physiological levels in vitro hold promise for future in vivo applications.
73. Lindahl T, Adams A, Bjursell G, Bornkamm GW, Kaschka-Dierich C, Jehn U: Covalently closed circular duplex DNA of Epstein-Barr virus in a human lymphoid cell line. J Mol Biol (1976) 102(3):511-530.
74. Wade-Martins R, White RE, Kimura H, Cook PR, James MR: Stable correction of a genetic deficiency in human cells by an episome carrying a 115 kb genomic transgene. Nat Biotechnol (2000) 18(12):1311-1314.
75. Wade-Martins R, Saeki Y, Chiocca EA: Infectious delivery of a 135-kb LDLR genomic locus leads to regulated complementation of low-density lipoprotein receptor deficiency in human cells. Mol Ther (2003) 7 (5 Pt 1) :604-612.
76. Xing W, Baylink D, Kesavan C, Mohan S: HSV-1 amplicon-mediated transfer of 128-kb BMP-2 genomic locus stimulates osteoblast differentiation in vitro. Biochem Biophys Res Commun (2004) 319(3):781-786.
77. Wilson JB, Levine AJ: The oncogenic potential of Epstein-Barr virus nuclear antigen 1 in transgenic mice. Curr Top Microbiol Immunol (1992) 182:375-384.
78. Pich D, Humme S, Spindler MP, Schepers A, Hammerschmidt W: Conditional gene vectors regulated in cis. Nucleic Acids Res (2008) 36(13) :e83.
79. Development of a new EBV vector that relies on a cellular protein high mobility group AT-hook protein 1 instead of a viral EBNA-1 protein for its replication.
80. Mirkovitch J, Mirault ME, Laemmli UK: Organization of the higher-order chromatin loop: Specific DNA attachment sites on nuclear scaffold. Cell (1984) 39(1):223-232.
81. Girod P-A, Mermod N: Use of scaffold/matrix-attachment regions for protein production. In: Gene Transfer and Expression in Mammalian Cells. Makrides SC (Ed) Elsevier Science BV, Amsterdam, Netherlands (2003):359-379.
82. Bode J, Benham C, Knopp A, Mielke C: Transcriptional augmentation: Modulation of gene expression by scaffold/matrix-attached regions (S/MAR elements). Crit Rev Eukaryot Gene Expr (2000) 10(1):73-90.
83. Bode J, Kohwi Y, Dickinson L, Joh T, Klehr D, Mielke C, Kohwi-Shigematsu T: Biological significance of unwinding capability of nuclear matrix-associating DNAs. Science (1992) 255 (5041): 195-197.
84. Bode J, Winkelmann S, Götze S, Spiker S, Tsutsui K, Bi C, A K P, Benham C: Correlations between scaffold/matrix attachment region (S/MAR) binding activity and DNA duplex destabilization energy. J Mol Biol (2006) 358(2):597-613.
85. von Kries JP, Phi-van L, Diekmann S, Strätling WH: A non-curved chicken lysozyme 5' matrix attachment site is 3' followed by a strongly curved DNA sequence. Nucleic Acids Res (1990) 18(13):3881-3885.
86. Giannakopoulos A, Stavrou EF, Zarkadis I, Zoumbos NC, Thrasher AJ, Athanassiadou A: The functional role of S/MARs in episomal vectors as defined by the stress-induced destabilization profile of the vector sequences. J Mol Biol (2009) 5(17):1239-1249.
87. Ohgane J, Yagi S, Shiota K: Epigenetics: The DNA methylation profile of tissue-dependent and differentially methylated regions in cells. Placenta (2008) 29 (Suppl A) :S29-S35.
88. Kalos M, Fournier R: Position-independant transgene expression mediated by boundary elements from the apoliprotein B chromatin domain. Mol Cell Biol (1995) 15(1):198-207.
89. Girod PA, Zahn-Zabal M, Mermod N: Use of the chicken lysozyme 5' matrix attachment region to generate high producer CHO cell lines. Biotechnol Bioeng (2005) 91(1):1-11.
90. Razin A, Webb C, Szyf M, Yisraeli J, Rosenthal A, Naveh-Many T, Sciaky-Gallili N, Cedar H: Variations in DNA methylation during mouse cell differentiation in vivo and in vitro. Proc Natl Acad Sci USA (1984) 81(8):2275-2279.
91. Bode J, Goetze S, Heng H, Krawetz SA, Benham C: From DNA structure to gene expression: Mediators of nuclear compartmentalization and dynamics. Chromosome Res (2003) 11(5):435-445.
92. Wiersma EJ, Ronai D, Berru M, Tsui FW, Shulman MJ: Role of the intronic elements in the endogenous immunoglobulin heavy chain locus. Either the matrix attachment regions or the core enhancer is sufficient to maintain expression. J Biol Chem (1999) 274(8):4858-4862.
93. Attal J, Cajero-Juarez M, Petitclerc D, Theron MC, Stinnakre MG, Bearzotti M, Kann G, Houdebine LM: The effect of matrix attached regions (MAR) and specialized chromatin structure (SCS) on the expression of gene constructs in cultured cells and in transgenic mice. Mol Biol Rep (1995) 22(1):37-46.
94. Makarova O, Gorneva G, Wu F, Farutin V, Villeponteau B, Poliani L, Fink D, Levine M: Incorporation of nuclear matrix attachment regions into the herpes simplex virus type 1 genome does not induce long-term expression of a foreign gene during latency. Gene Ther (1996) 3(9):829-833.
95. Piechaczek C, Fetzer C, Baiker A, Bode J, Lipps HJ: A vector based on the SV40 origin of replication and chromosomal S/MARs replicates episomally in CHO cells. Nucleic Acids Res (1999) 27(2):426-428.
96. Jenke BH, Fetzer CP, Stehle IM, Jönsson F, Fackelmayer FO, Conradt H, Bode J, Lipps HJ: An episomally replicating vector binds to the nuclear matrix protein SAF-A in vivo. EMBO Rep (2002) 3(4):349-354.
97. Goetze S, Baer A, Winkelmann S, Nehlsen K, Seibler J, Maass K, Bode J: Performance of genomic bordering elements at predefined genomic loci. Mol Cell Biol (2005) 25(6):2260-2272.
98. Bode J, Schlake T, Rios-Ramirez M, Mielke C, Stengert M, Kay V, Klehr-Wirth D: Scaffold/matrix-attached regions: Structural properties creating transcriptionally active loci. Int Rev Cytol (1995) 162A:389-454.
99. Romig H, Fackelmayer FO, Renz A, Ramsperger U, Richter A: Characterization of SAF-A, a novel nuclear DNA binding protein from HeLa cells with high affnity for nuclear matrix/scaffold attachment DNA elements. EMBO J (1992) 11(9):3431-3440.
100. Martens JH, Verlaan M, Kalkhoven E, Dorsman JC, Zantema A: Scaffold/matrix attachment region elements interact with a p300-scaffold attachment factor A complex and are bound by acetylated nucleosomes. Mol Cell Biol (2002) 22(8):2598-2606.
101. Nayler O, Strätling W, Bourquin JP, Stagljar I, Lindemann L, Jasper H, Hartmann AM, Fackelmayer FO, Ullrich A, Stamm S: SAF-B protein couples transcription and pre-mRNA splicing to SAR/MAR elements. Nucleic Acids Res (1998) 26(15):3542-3549.
102. von Kries JP, Buhrmester H, Strätling WH: A matrix/scaffold attachment region binding protein: Identification, purification, and mode of binding. Cell (1991) 64(1):123-135.
103. Galande S, Purbey PK, Notani D, Kumar PP: The third dimension of gene regulation: Organization of dynamic chromatin loopscape by SATB1. Curr Opin Genet Dev (2007) 17(5):408-414.
104. Dickinson LA, Joh T, Kohwi Y, Kohwi-Shigematsu T: A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition. Cell (1992) 70(4):631-645.
105. Jenke AC, Stehle IM, Herrmann F, Eisenberger T, Baiker A, Bode J, Fackelmayer FO, Lipps HJ: Nuclear scaffold/matrix attached region modules linked to a transcription unit are sufficient for replication and maintenance of a mammalian episome. Proc Natl Acad Sci USA (2004) 101(31):11322-11327.
106. Stehle IM, Scinteie MF, Baiker A, Jenke AC, Lipps HJ: Exploiting a minimal system to study the epigenetic control of DNA replication: The interplay between transcription and replication. Chromosome Res (2003) 11(5):413-421.
107. Baiker A, Maercker C, Piechaczek C, Schmidt SB, Bode J, Benham C, Lipps HJ: Mitotic stability of an episomal vector containing a human scaffold/matrix-attached region is provided by association with nuclear matrix. Nat Cell Biol (2000) 2(3):182-184.
108. Stehle IM, Postberg J, Rupprecht S, Cremer T, Jackson DA, Lipps HJ: Establishment and mitotic stability of an extra-chromosomal mammalian replicon. BMC Cell Biol (2007) 8:33.
109. Schaarschmidt D, Baltin J, Stehle IM, Lipps HJ, Knippers R: An episomal mammalian replicon: Sequence-independent binding of the origin recognition complex. EMBO J (2004) 23(1): 191-201.
110. Papapetrou EP, Ziros PG, Micheva ID, Zoumbos NC, Athanassiadou A: Gene transfer into human hematopoietic progenitor cells with an episomal vector carrying an S/MAR element. Gene Ther (2006) 13(1):40-51.
111. Sotirova VN, Calciano MA, Krueger W, Lalande M: Inclusion of a matrix-attached region in a 7SK pol III vector increases the efficiency of shRNA-mediated gene silencing in embryonic carcinoma cells. Plasmid (2006) 55(3):216-226.
112. Jenke AC, Eisenberger T, Baiker A, Stehle IM, Wirth S, Lipps HJ: The nonviral episomal replicating vector pEPI-1 allows long-term inhibition of BCR-ABL expression by shRNA. Hum Gene Ther (2005) 16(4):533-539.
113. Jenke AC, Wilhelm AD, Orth V, Lipps HJ, Protzer U, Wirth S: Longterm suppression of hepatitis B virus replication by short hairpin RNA expression using the scaffold/matrix attachment region-based replicating vector system pEPI-1. Antimicrob Agents Chemother (2008) 52(7):2355-2359.
114. Manzini S, Vargiolu A, Stehle IM, Bacci ML, Cerrito MG, Giovannoni R, Zannoni A, Bianco MR, Forni M, Donini P, Papa M et al: Genetically modified pigs produced with a nonviral episomal vector. Proc Natl Acad Sci USA (2006) 103(47):17672-17677.
115. Argyros O, Wong SP, Niceta M, Waddington SN, Howe SJ, Coutelle C, Miller AD, Harbottle RP: Persistent episomal transgene expression in liver following delivery of a scaffold/matrix attachment region containing non-viral vector. Gene Ther (2008) 15(24):1593-1605.
116. The first to describe long-term persistent expression in the liver following hydrodynamic delivery of a tissue-specific plasmid in combination with the S/MAR element.
117. Ehrhardt A, Haase R, Schepers A, Deutsch MJ, Lipps HJ, Baiker A: Episomal vectors for gene therapy. Curr Gene Ther (2008) 8(3):147-161.
118. Nehlsen K, Broll S, Bode J: Replicating minicircles: Generation of nonviral episomes for the efficient modification of dividing cells. Gene Ther Mol Biol (2006) 10:233-244.
119. Gallaher SD, Gil JS, Dorigo O, Berk AJ: Robust in vivo transduction of a genetically stable Epstein-Barr virus episome to hepatocytes in mice by a hybrid viral vector. Journal of Virology (2009) 83(7):3249-3257.