6 Conclusions
Currently, significant advances in the development of non-viral vectors are being made by means of recent technological innovations, including nanotechnology (Vijayanathan et al. 2002). Employment of functional genetic elements, such as EBNA1/oriP and the SB transposon, may further improve their efficacy, compensating for the shortcomings of non-viral systems. EBV-based plasmid vectors are transported into and maintained in the nucleus as well as replicated as episomes, overcoming the problems of the low transfection rate and the transience of transgene expression. The SB transposon enables chromosomal integration of a transgene in transfected cells, potentially enabling its permanent expression, although random integration into the host genome may cause aberrant expression and/or silencing of cellular genes that locate close to the integration site. Both the EBV-based plasmid vector and SB have been shown to work not only in vitro but also in vivo. Plasmid vector sequences should be focused on as an important component of non-viral gene delivery systems, while their combination with other devises, such as polypeptides containing a nuclear localization signal (reviewed in Hebert 2003), may also be useful in developing promising strategies.
Keywords
- Plasmid Vector
- Sleep Beauty
- Junctional Epidermolysis Bullosa
- Sleep Beauty Transposition
- Base Plasmid Vector
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Adams A (1987) Replication of latent Epstein-Barr virus genomes in Raji cells. J Virol 61:1743–1746
Ambinder RF, Mullen MA, Chang YN, Hayward GS, Hayward SD (1991) Functional domains of Epstein-Barr virus nuclear antigen EBNA-1. J Virol 65:1466–1478
Asada H, Kishida T, Hirai H, Satoh E, Ohashi S, Takeuchi M, Kubo T, Kita M, Iwakura Y, Imanishi J, Mazda O (2002) Significant antitumor effects obtained by autologous tumor cell vaccine engineered to secrete interleukin-12 (IL-12) and IL-18 by means of the EBV/lipoplex. Mol Ther 5:609–616
Belur LR, Frandsen JL, Dupuy AJ, Ingbar DH, Largaespada DA, Hackett PB, Scott McIvor R (2003) Gene insertion and long-term expression in lung mediated by the Sleeping Beauty transposon system. Mol Ther 8:501–507
Black J, Vos JM (2002) Establishment of an oriP/EBNA1-based episomal vector transcribing human genomic beta-globin in cultured murine fibroblasts. Gene Ther 9:1447–1454
Cui FD, Kishida T, Ohashi S, Asada H, Yasutomi K, Satoh E, Kubo T, Fushiki S, Imanishi J, Mazda O (2001) Highly efficient gene transfer into murine liver achieved by intravenous administration of naked Epstein-Barr virus (EBV)-based plasmid vectors. Gene Ther 8:1508–1513
Cui FD, Asada H, Kishida T, Itokawa Y, Nakaya T, Ueda Y, Yamagishi H, Gojo S, Kita M, Imanishi J, Mazda O (2003) Intravascular naked DNA vaccine encoding glycoprotein B induces protective humoral and cellular immunity against herpes simplex virus type 1 infection in mice. Gene Ther 10:2059–2066
Cui FD, Asada H, Jin ML, Kishida T, Shin-Ya M, Nakaya T, Kita M, Ishii M, Iwai M, Okanoue T, Imanishi J, Mazda O (2005) Cytokine genetic adjuvant facilitates prophylactic intravascular DNA vaccine against acute and latent herpes simplex virus infection in mice. Gene Ther 12:160–168
Cui Z, Mumper RJ (2003) Microparticles and nanoparticles as delivery systems for DNA vaccines. Crit Rev Ther Drug Carrier Syst 20:103–137
Dupuy AJ, Clark K, Carlson CM, Fritz S, Davidson AE, Markley KM, Finley K, Fletcher CF, Ekker SC, Hackett PB, Horn S, Largaespada DA (2002) Mammalian germ-line transgenesis by transposition. Proc Natl Acad Sci U S A 99:4495–4499
Felgner PL, Ringold GM (1989) Cationic liposome-mediated transfection. Nature 337:387–388
Fischer N, Kremmer E, Lautscham G, Mueller-Lantzsch N, Grasser FA (1997) Epstein-Barr virus nuclear antigen 1 forms a complex with the nuclear transporter karyopherin alpha2. J Biol Chem 272:3999–4005
Fischer SE, Wienholds E, Plasterk RH (2001) Regulated transposition of a fish transposon in the mouse germ line. Proc Natl Acad Sci U S A 98:6759–6764
Gahn TA, Sugden B (1995) An EBNA-1-dependent enhancer acts from a distance of 10 kilobase pairs to increase expression of the Epstein-Barr virus LMP gene. J Virol 69:2633–2636
Haase SB, Calos MP (1991) Replication control of autonomously replicating human sequences. Nucleic Acids Res 19:5053–5058
Harada Y, Iwai M, Tanaka S, Okanoue T, Kashima K, Maruyama-Tabata H, Hirai H, Satoh E, Imanishi J, Mazda O (2000) Highly efficient suicide gene expression in hepatocellular carcinoma cells by Epstein-Barr virus-based plasmid vectors combined with polyamidoamine dendrimer. Cancer Gene Ther 7:27–36
Harris JW, Strong DD, Amoui M, Baylink DJ, Lau KH (2002) Construction of a Tc1-like transposon Sleeping Beauty-based gene transfer plasmid vector for generation of stable transgenic mammalian cell clones. Anal Biochem 310:15–26
Hebert E (2003) Improvement of exogenous DNA nuclear importation by nuclear localization signal-bearing vectors: a promising way for non-viral gene therapy? Biol Cell 95:59–68
Herweijer H, Wolff JA (2003) Progress and prospects: naked DNA gene transfer and therapy. Gene Ther 10:453–458
Hirai H, Satoh E, Osawa M, Inaba T, Shimazaki C, Kinoshita S, Nakagawa M, Mazda O, Imanishi J (1997) Use of EBV-based Vector/HVJ-liposome complex vector for targeted gene therapy of EBV-associated neoplasms. Biochem Biophys Res Commun 241:112–118
Horie K, Yusa K, Yae K, Odajima J, Fischer SE, Keng VW, Hayakawa T, Mizuno S, Kondoh G, Ijiri T, Matsuda Y, Plasterk RH, Takeda J (2003) Characterization of Sleeping Beauty transposition and its application to genetic screening in mice. Mol Cell Biol 23:9189–9207
Hosseinkhani H, Aoyama T, Ogawa O, Tabata Y (2003) Ultrasound enhances the transfection of plasmid DNA by non-viral vectors. Curr Pharm Biotechnol 4:109–122
Itokawa Y, Mazda O, Ueda Y, Kishida T, Asada H, Cui FD, Fuji N, Fujiwara H, Shin-Ya M, Yasutomi K, Imanishi J, Yamagishi H (2004) Interleukin-12 genetic administration suppressed metastatic liver tumor unsusceptible to CTL. Biochem Biophys Res Commun 314:1072–1079
Ivics Z, Izsvak Z (2004) Transposable elements for transgenesis and insertional mutagenesis in vertebrates: a contemporary review of experimental strategies. Methods Mol Biol 260:255–276
Ivics Z, Hackett PB, Plasterk RH, Izsvak Z (1997) Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell 91:501–510
Iwai M, Harada Y, Tanaka S, Muramatsu A, Mori T, Kashima K, Imanishi J, Mazda O (2002) Polyethylenimine-mediated suicide gene transfer induces a therapeutic effect for hepatocellular carcinoma in vivo by using an Epstein/Barr virus-based plasmid vector. Biochem Biophys Res Commun 291:48–54
Izsvak Z, Ivics Z (2004) Sleeping beauty transposition: biology and applications for molecular therapy. Mol Ther 9:147–156
Izsvak Z, Ivics Z, Plasterk RH (2000) Sleeping Beauty, a wide host-range transposon vector for genetic transformation in vertebrates. J Mol Biol 302:93–102
Jankelevich S, Kolman JL, Bodnar JW, Miller G (1992) A nuclear matrix attachment region organizes the Epstein-Barr viral plasmid in Raji cells into a single DNA domain. EMBO J 11:1165–1176
Kelleher ZT, Fu H, Livanos E, Wendelburg B, Gulino S, Vos JM (1998) Epstein-Barr-based episomal chromosomes shuttle 100kb of self-replicating circular human DNA in mouse cells. Nat Biotechnol 16:762–768.
Kishida T, Asada H, Satoh E, Tanaka S, Shinya M, Hirai H, Iwai M, Tahara H, Imanishi J, Mazda O (2001) In vivo electroporation-mediated transfer of interleukin-12 and interleukin-18 genes induces significant antitumor effects against melanoma in mice. Gene Ther 8:1234–1240
Kishida T, Asada H, Itokawa Y, Cui FD, Shin-Ya M, Gojo S, Yasutomi K, Ueda Y, Yamagishi H, Imanishi J, Mazda O (2003a) Interleukin (IL)-21 and IL-15 genetic transfer synergistically augments therapeutic antitumor immunity and promotes regression of metastatic lymphoma. Mol Ther 8:552–558
Kishida T, Asada H, Itokawa Y, Yasutomi K, Shin-Ya M, Gojo S, Cui FD, Ueda Y, Yamagishi H, Imanishi J, Mazda O (2003b) Electrochemo-gene therapy of cancer: intratumoral delivery of interleukin-12 gene and bleomycin synergistically induced therapeutic immunity and suppressed subcutaneous and metastatic melanomas in mice. Mol Ther 8:738–745
Kukowska-Latallo JF, Bielinska AU, Johnson J, Spindler R, Tomalia DA, Baker JR, Jr. (1996) Efficient transfer of genetic material into mammalian cells using Starburst polyamidoamine dendrimers. Proc Natl Acad Sci U S A 93:4897–4902
Kumar VV, Singh RS, Chaudhuri A (2003) Cationic transfection lipids in gene therapy: successes, set-backs, challenges and promises. Curr Med Chem 10:1297–1306
Lechardeur D, Lukacs GL (2002) Intracellular barriers to non-viral gene transfer. Curr Gene Ther 2:183–194
Lemkine GF, Demeneix BA (2001) Polyethylenimines for in vivo gene delivery. Curr Opin Mol Ther 3:178–182
Liu G, Aronovich EL, Cui Z, Whitley CB, Hackett PB (2004a) Excision of Sleeping Beauty transposons: parameters and applications to gene therapy. J Gene Med 6:574–583
Liu L, Sanz S, Heggestad AD, Antharam V, Notterpek L, Fletcher BS (2004b) Endothelial targeting of the Sleeping Beauty transposon within lung. Mol Ther 10:97–105
Maruyama-Tabata H, Harada Y, Matsumura T, Satoh E, Cui F, Iwai M, Kita M, Hibi S, Imanishi J, Sawada T, Mazda O (2000) Effective suicide gene therapy in vivo by EBVbased plasmid vector coupled with polyamidoamine dendrimer. Gene Ther 7:53–60
Mazda O (2000) Application of Epstein-Barr virus (EBV) and its genetic elements to gene therapy. In: Cid-Arregui A, Garcia-Carranca A (Eds) Viral Vectors: Basic Science and Gene Therapy. Eaton Publishing, Natick, MA. pp 325–337
Mazda O (2002) Improvement of non-viral gene therapy by Epstein-Barr virus (EBV)-based plasmid vectors. Curr Gene Ther 2:379–392
Mazda O, Satoh E, Yasutomi K, Imanishi J (1997) Extremely efficient gene transfection into lympho-hematopoietic cell lines by Epstein-Barr virus-based vectors. J Immunol Methods 204:143–151
Mikkelsen JG, Yant SR, Meuse L, Huang Z, Xu H, Kay MA (2003) Helper-Independent Sleeping Beauty transposon-transposase vectors for efficient non-viral gene delivery and persistent gene expression in vivo. Mol Ther 8:654–665
Montini E, Held PK, Noll M, Morcinek N, Al-Dhalimy M, Finegold M, Yant SR, Kay MA, Grompe M (2002) In vivo correction of murine tyrosinemia type I by DNA-mediated transposition. Mol Ther 6:759–769
Nakanishi H, Mazda O, Satoh E, Asada H, Morioka H, Kishida T, Nakao M, Mizutani Y, Kawauchi A, Kita M, Imanishi J, Miki T (2003) Non-viral genetic transfer of Fas ligand induced significant growth suppression and apoptotic tumor cell death in prostate cancer in vivo. Gene Ther 10:434–442
Niidome T, Huang L (2002) Gene therapy progress and prospects: non-viral vectors. Gene Ther 9:1647–1652
Ohashi S, Kubo T, Ikeda T, Arai Y, Takahashi K, Hirasawa Y, Takigawa M, Satoh E, Imanishi J, Mazda O (2001) Cationic polymer-mediated genetic transduction into cultured human chondrosarcoma-derived HCS-2/8 cells. J Orthop Sci 6:75–81
Ohashi S, Kubo T, Kishida T, Ikeda T, Takahashi K, Arai Y, Terauchi R, Asada H, Imanishi J, Mazda O (2002) Successful genetic transduction in vivo into synovium by means of electroporation. Biochem Biophys Res Commun 293:1530–1535
Ortiz-Urda S, Lin Q, Yant SR, Keene D, Kay MA, Khavari PA (2003) Sustainable correction of junctional epidermolysis bullosa via transposon-mediated non-viral gene transfer. Gene Ther 10:1099–1104
Plank C, Anton M, Rudolph C, Rosenecker J, Krotz F (2003) Enhancing and targeting nucleic acid delivery by magnetic force. Expert Opin Biol Ther 3:745–758
Puglielli MT, Woisetschlaeger M, Speck SH (1996) oriP is essential for EBNA gene promoter activity in Epstein-Barr virus-immortalized lymphoblastoid cell lines. J Virol 70:5758–5768
Raz E, van Luenen HG, Schaerringer B, Plasterk RH, Driever W (1998) Transposition of the nematode Caenorhabditis elegans Tc3 element in the zebrafish Danio rerio. Curr Biol 8:82–88
Reisman D, Sugden B (1986) trans activation of an Epstein-Barr viral transcriptional enhancer by the Epstein-Barr viral nuclear antigen 1. Mol Cell Biol 6:3838–3846
Roberg-Perez K, Carlson CM, Largaespada DA (2003) MTID: a database of Sleeping Beauty transposon insertions in mice. Nucleic Acids Res 31:78–81
Rocha A, Ruiz S, Coll JM (2002) Improvement of DNA transfection with cationic liposomes. J Physiol Biochem 58:45–56
Satoh E, Hirai H, Inaba T, Shimazaki C, Nakagawa M, Imanishi J, Mazda O (1998) Successful transfer of ADA gene in vitro into human peripheral blood CD34+ cells by transfecting EBV-based episomal vectors. FEBS Lett 441:39–42
Satoh E, Osawa M, Tomiyasu K, Hirai H, Shimazaki C, Oda Y, Nakagawa M, Kondo M, Kinoshita S, Mazda O, Imanishi J (1997) Efficient gene transduction by Epstein-Barrvirus-based vectors coupled with cationic liposome and HVJ-liposome. Biochem Biophys Res Commun 238:795–799
Sclimenti CR, Neviaser AS, Baba EJ, Meuse L, Kay MA, Calos MP (2003) Epstein-Barr virus vectors provide prolonged robust factor IX expression in mice. Biotechnol Prog 19:144–151
Stoll SM, Calos MP (2002) Extrachromosomal plasmid vectors for gene therapy. Curr Opin Mol Ther 4:299–305
Stoll SM, Sclimenti CR, Baba EJ, Meuse L, Kay MA, Calos MP (2001) Epstein-Barr Virus/Human Vector Provides High-Level, Long-Term Expression of alpha(1)-Antitrypsin in Mice. Mol Ther 4:122–129.
Sugden B, Warren N (1989) A promoter of Epstein-Barr virus that can function during latent infection can be transactivated by EBNA-1, a viral protein required for viral DNA replication during latent infection. J Virol 63:2644–2649
Sun TQ, Fernstermacher DA, Vos JM (1994) Human artificial episomal chromosomes for cloning large DNA fragments in human cells [published erratum appears in Nat Genet 1994 Dec;8(4):410]. Nat Genet 8:33–41
Tanaka S, Iwai M, Harada Y, Morikawa T, Muramatsu A, Mori T, Okanoue T, Kashima K, Maruyama-Tabata H, Hirai H, Satoh E, Imanishi J, Mazda O (2000) Targeted killing of carcinoembryonic antigen (CEA)-producing cholangiocarcinoma cells by polyamidoamine dendrimer-mediated transfer of an Epstein-Barr virus (EBV)-based plasmid vector carrying the CEA promoter. Cancer Gene Ther 7:1241–1250
Tang MX, Redemann CT, Szoka FC, Jr. (1996) In vitro gene delivery by degraded polyamidoamine dendrimers. Bioconjug Chem 7:703–714
Tomiyasu K, Satoh E, Oda Y, Nishizaki K, Kondo M, Imanishi J, Mazda O (1998) Gene transfer in vitro and in vivo with Epstein-Barr virus-based episomal vector results in markedly high transient expression in rodent cells. Biochem Biophys Res Commun 253:733–738
Tomiyasu K, Oda Y, Nomura M, Satoh E, Fushiki S, Imanishi J, Kondo M, Mazda O (2000) Direct intra-cardiomuscular transfer of beta2-adrenergic receptor gene augments cardiac output in cardiomyopathic hamsters. Gene Ther 7:2087–2093
Vigdal TJ, Kaufman CD, Izsvak Z, Voytas DF, Ivics Z (2002) Common physical properties of DNA affecting target site selection of sleeping beauty and other Tc1/mariner transposable elements. J Mol Biol 323:441–452
Vijayanathan V, Thomas T, Thomas TJ (2002) DNA nanoparticles and development of DNA delivery vehicles for gene therapy. Biochemistry 41:14085–14094
Westphal EM, Sierakowska H, Livanos E, Kole R, Vos JM (1998) A system for shuttling 200-kb BAC/PAC clones into human cells: stable extrachromosomal persistence and long-term ectopic gene activation. Hum Gene Ther 9:1863–1873
Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247:1465–1468.
Wysokenski DA, Yates JL (1989) Multiple EBNA1-binding sites are required to form an EBNA1-dependent enhancer and to activate a minimal replicative origin within oriP of Epstein-Barr virus. J Virol 63:2657–2666
Yant SR, Meuse L, Chiu W, Ivics Z, Izsvak Z, Kay MA (2000) Somatic integration and longterm transgene expression in normal and haemophilic mice using a DNA transposon system. Nat Genet 25:35–41
Yasutomi K, Itokawa Y, Asada H, Kishida T, Cui FD, Ohashi S, Gojo S, Ueda Y, Kubo T, Yamagishi H, Imanishi J, Takeuchi T, Mazda O (2003) Intravascular insulin gene delivery as potential therapeutic intervention in diabetes mellitus. Biochem Biophys Res Commun 310:897–903
Yates JL, Guan N (1991) Epstein-Barr virus-derived plasmids replicate only once per cell cycle and are not amplified after entry into cells. J Virol 65:483–488
Zagoraiou L, Drabek D, Alexaki S, Guy JA, Klinakis AG, Langeveld A, Skavdis G, Mamalaki C, Grosveld F, Savakis C (2001) In vivo transposition of Minos, a Drosophila mobile element, in mammalian tissues. Proc Natl Acad Sci U S A 98:11474–11478
Zayed H, Izsvak Z, Walisko O, Ivics Z (2004) Development of hyperactive sleeping beauty transposon vectors by mutational analysis. Mol Ther 9:292–304
Zayed H, Izsvak Z, Khare D, Heinemann U, Ivics Z (2003) The DNA-bending protein HMGB1 is a cellular cofactor of Sleeping Beauty transposition. Nucleic Acids Res 31:2313–2322
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Springer-Verlag Tokyo
About this chapter
Cite this chapter
Mazda, O., Kishida, T. (2005). Functional Nucleotide Sequences Capable of Promoting Non-viral Genetic Transfer. In: Taira, K., Kataoka, K., Niidome, T. (eds) Non-viral Gene Therapy. Springer, Tokyo. https://doi.org/10.1007/4-431-27879-6_16
Download citation
DOI: https://doi.org/10.1007/4-431-27879-6_16
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-25122-4
Online ISBN: 978-4-431-27879-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)