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Plasmid Biopharmaceuticals

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  • Authors: Duarte Miguel F. Prazeres1, Gabriel A. Monteiro2
  • Editors: Marcelo E. Tolmasky3, Juan Carlos Alonso4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: IBB, Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal; 2: IBB, Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal; 3: California State University, Fullerton, CA; 4: Centro Nacional de Biotecnología, Cantoblanco, Madrid, Spain
  • Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.PLAS-0022-2014
  • Received 08 November 2013 Accepted 16 December 2013 Published 07 November 2014
  • Duarte Miguel F. Prazeres, miguelprazeres@ist.utl.pt
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  • Abstract:

    Plasmids are currently an indispensable molecular tool in life science research and a central asset for the modern biotechnology industry, supporting its mission to produce pharmaceutical proteins, antibodies, vaccines, industrial enzymes, and molecular diagnostics, to name a few key products. Furthermore, plasmids have gradually stepped up in the past 20 years as useful biopharmaceuticals in the context of gene therapy and DNA vaccination interventions. This review provides a concise coverage of the scientific progress that has been made since the emergence of what are called today plasmid biopharmaceuticals. The most relevant topics are discussed to provide researchers with an updated overview of the field. A brief outline of the initial breakthroughs and innovations is followed by a discussion of the motivation behind the medical uses of plasmids in the context of therapeutic and prophylactic interventions. The molecular characteristics and rationale underlying the design of plasmid vectors as gene transfer agents are described and a description of the most important methods used to deliver plasmid biopharmaceuticals (gene gun, electroporation, cationic lipids and polymers, and micro- and nanoparticles) is provided. The major safety issues (integration and autoimmunity) surrounding the use of plasmid biopharmaceuticals is discussed next. Aspects related to the large-scale manufacturing are also covered, and reference is made to the plasmid products that have received marketing authorization as of today.

  • Citation: Prazeres D, Monteiro G. 2014. Plasmid Biopharmaceuticals. Microbiol Spectrum 2(6):PLAS-0022-2014. doi:10.1128/microbiolspec.PLAS-0022-2014.

Key Concept Ranking

Gene Expression and Regulation
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References

1. Cohen SN, Chang AC, Boyer HW, Helling RB. 1973. Construction of biologically functional bacterial plasmids in vitro. Proc Natl Acad Sci USA 70:3240–3244. [PubMed][CrossRef]
2. Russo E. 2003. Special report: the birth of biotechnology. Nature 421:456–457. [PubMed][CrossRef]
3. Hughes SS. 2001. Making dollars out of DNA: the first major patent in biotechnology and the commercialization of molecular biology, 1974–1980. Isis 92:541–575. [PubMed][CrossRef]
4. Prazeres DMF. 2011. Historical perspective, p 3–34. In Plasmid Biopharmaceuticals: Basics Applications and Manufacturing. John Wiley & Sons, Inc., Hoboken, NJ. [CrossRef]
5. 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. [PubMed][CrossRef]
6. Hickman MA, Malone RW, Lehmann-Bruinsma K, Sih TR, Knoell D, Szoka FC, Walzem R, Carlson DM, Powell JS. 1994. Gene expression following direct injection of DNA into liver. Hum Gene Ther 5:1477–1483. [PubMed][CrossRef]
7. Ardehali A, Fyfe A, Laks H, Drinkwater DC, Qiao J-H, Lusis AJ. 1995. Direct gene transfer into donor hearts at the time of harvest. J Thor Cardiovasc Surg. 109:716–720. [CrossRef]
8. Schwartz B, Benoist C, Abdallah B, Rangara R, Hassan A, Scherman D, Demeneix BA. 1996. Gene transfer by naked DNA into adult mouse brain. Gene Ther 3:405–411. [PubMed]
9. Hansen E, Fernandes K, Goldspink G, Butterworth P, Umeda PK, Chang KC. 1991. Strong expression of foreign genes following direct injection into fish muscle. FEBS Lett 290:73–76. [PubMed][CrossRef]
10. Fynan EF, Webster RG, Fuller DH, Haynes JR, Santoro JC, Robinson HL. 1993. DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc Natl Acad Sci USA 90:11478–11482. [PubMed][CrossRef]
11. Cox GJ, Zamb TJ, Babiuk LA. 1993. Bovine herpesvirus 1: immune responses in mice and cattle injected with plasmid DNA. J Virol 67:5664–5667. [PubMed]
12. Tang DC, DeVit M, Johnston SA. 1992. Genetic immunization is a simple method for eliciting an immune response. Nature 356:152–154. [PubMed][CrossRef]
13. Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Felgner PL, Dwarki VJ, Gromkowski SH, Deck RR, Dewitt CM, Friedman A, Hawe LA, Leander KR, Martinez D, Perry HC, Shiver JW, Montgomery DL, Liu MA. 1993. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259:1745–1749. [PubMed][CrossRef]
14. Prazeres DMF. 2011. Concluding remarks and outlook, p 565–578. In Plasmid Biopharmaceuticals: Basics Applications and Manufacturing. John Wiley & Sons, Inc., Hoboken, NJ.
15. Yang NS, Burkholder J, Roberts B, Martinell B, McCabe D. 1990. In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment. Proc Natl Acad Sci USA 87:9568–9572. [PubMed][CrossRef]
16. Titomirov AV, Sukharev S, Kistanova E. 1991. In vivo electroporation and stable transformation of skin cells of newborn mice by plasmid DNA. Biochim Biophys Acta 1088:131–134. [PubMed][CrossRef]
17. Xiang Z, Ertl HC. 1995. Manipulation of the immune response to a plasmid-encoded viral antigen by coinoculation with plasmids expressing cytokines. Immunity 2:129–135. [PubMed][CrossRef]
18. Sato Y, Roman M, Tighe H, Lee D, Corr M, Nguyen MD, Silverman GJ, Lotz M, Carson DA, Raz E. 1996. Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science 273:352–354. [PubMed][CrossRef]
19. Davies HL, Mancini M, Michel M-L, Whalen RG. 1996. DNA-mediated immunization to hepatitis B surface antigen: longevity of primary response and effect of boost. Vaccine 14:910–915. [PubMed][CrossRef]
20. Ciernik IF, Berzofsky JA, Carbone DP. 1996. Induction of cytotoxic T lymphocytes and antitumor immunity with DNA vaccines expressing single T cell epitopes. J Immunol 156:2369–2375. [PubMed]
21. Jones DH, Corris S, McDonald S, Clegg JCS, Farrar GH. 1997. Poly(DL-lactide-co-glycolide)-encapsulated plasmid DNA elicits systemic and mucosal antibody responses to encoded protein after oral administration. Vaccine 15:814–817. [PubMed][CrossRef]
22. Darquet AM, Cameron B, Wils P, Scherman D, Crouzet J. 1997. A new DNA vehicle for nonviral gene delivery: supercoiled minicircle. Gene Ther 4:1341–1349. [PubMed][CrossRef]
23. Perales JC, Grossmann GA, Molas M, Liu G, Ferkol T, Harpst J, Oda H, Hanson RW. 1997. Biochemical and functional characterization of DNA complexes capable of targeting genes to hepatocytes via the asialoglycoprotein receptor. J Biol Chem 272:7398–7407. [PubMed][CrossRef]
24. Liu F, Song Y, Liu D. 1999. Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA. Gene Ther 6:1258–1266. [PubMed][CrossRef]
25. Raper SE, Chirmule N, Lee FS, Wivel NA, Bagg A, Gao GP, Wilson JM, Batshaw ML. 2003. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab 80:148–158. [PubMed][CrossRef]
26. Prazeres DMF. 2011. Gene transfer with plasmid biopharmaceuticals, p 35–68. In Plasmid Biopharmaceuticals: Basics Applications and Manufacturing. John Wiley & Sons, Inc., Hoboken, NJ. [CrossRef]
27. Zhong J, Eliceiri B, Stupack D, Penta K, Sakamoto G, Quertermous T, Coleman M, Boudreau N, Varner JA. 2003. Neovascularization of ischemic tissues by gene delivery of the extracellular matrix protein Del-1. J Clin Invest 112:30–41. [PubMed][CrossRef]
28. Koike H, Ishida A, Shimamura M, Mizuno S, Nakamura T, Ogihara T, Kaneda Y, Morishita R. 2006. Prevention of onset of Parkinson's disease by in vivo gene transfer of human hepatocyte growth factor in rodent model: a model of gene therapy for Parkinson's disease. Gene Ther 13:1639–1644. [PubMed][CrossRef]
29. Alton EW, Stern M, Farley R, Jaffe A, Chadwick SL, Phillips J, Davies J, Smith SN, Browning J, Davies MG, Hodson ME, Durham SR, Li D, Jeffery PK, Scallan M, Balfour R, Eastman SJ, Cheng SH, Smith AE, Meeker D, Geddes DM. 1999. Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial. Lancet 353:947–954. [PubMed][CrossRef]
30. Romero NB, Braun S, Benveniste O, Braun S, Benveniste O, Leturcq F, Hogrel JY, Morris GE, Barois A, Eymard B, Payan C, Ortega V, Boch AL, Lejean L, Thioudellet C, Mourot B, Escot C, Choquel A, Recan D, Kaplan JC, Dickson G, Klatzmann D, Molinier-Frenckel V, Guillet JG, Squiban P, Herson S, Fardeau M. 2004. Phase I study of dystrophin plasmid-based gene therapy in Duchenne/Becker muscular dystrophy. Hum Gene Ther 15:1065–1076. [PubMed][CrossRef]
31. Croze F, Prud'homme GJ. 2003. Gene therapy of streptozotocin-induced diabetes by intramuscular delivery of modified preproinsulin genes. J Gene Med 5:425–437. [PubMed][CrossRef]
32. Sebestyén MG, Hegge JO, Noble MA, Lewis DL, Herweijer H, Wolff JA. 2007. Progress toward a nonviral gene therapy protocol for the treatment of anemia. Hum Gene Ther 18:269–285. [PubMed][CrossRef]
33. Ferraro B, Morrow MP, Hutnick NA, Shin TH, Lucke CE, Weiner DB. 2011. Clinical applications of DNA vaccines: current progress. Clin Infect Dis 53:296–302. [PubMed][CrossRef]
34. Giri M, Ugen KE, Weiner DB. 2004. DNA vaccines against human immunodeficiency virus type 1 in the past decade. Clin Microbiol Rev 17:370–389. [PubMed][CrossRef]
35. Rainczuk A, Scorza T, Spithill TW, Smooker PM. 2004. A bicistronic DNA vaccine containing apical membrane antigen 1 and merozoite surface protein 4/5 can prime humoral and cellular immune responses and partially protect mice against virulent Plasmodium chabaudi adami DS malaria. Infect Immun 72:5565–5573. [PubMed][CrossRef]
36. Haile M, Kallenius G. 2005. Recent developments in tuberculosis vaccines. Curr Opin Infect Dis 18:211–215. [PubMed][CrossRef]
37. Drape RJ, Macklin MD, Barr LJ, Jones S, Haynes JR, Dean HJ. 2006. Epidermal DNA vaccine for influenza is immunogenic in humans. Vaccine 24:4475–4481. [PubMed][CrossRef]
38. Lowe DB, Shearer MH, Kennedy RC. 2006. DNA vaccines: successes and limitations in cancer and infectious disease. J Cell Biochem 98:235–242. [PubMed][CrossRef]
39. Kaykas A, Moon RT. 2004. A plasmid-based system for expressing small interfering RNA libraries in mammalian cells. BMC Cell Biol 5:16. doi:10.1186/1471-2121-5-16. [PubMed][CrossRef]
40. Zeitelhofer M, Karra D, Vessey JP, Jaskic E, Macchi P, Thomas S, Riefler J, Kiebler M, Dahm R. 2009. High-efficiency transfection of short hairpin RNAs-encoding plasmids into primary hippocampal neurons. J Neurosci Res 87:289–300. [PubMed][CrossRef]
41. Li Z, Yang S, Chang T, Cao X, Shi L, Fang G. 2012. Anti-angiogenesis and anticancer effects of a plasmid expressing both ENDO-VEGI151 and small interfering RNA against surviving. Int J Mol Med 29:485–490. [PubMed]
42. Fewell JG, MacLaughlin F, Mehta V, Gondo M, Nicol F, Wilson E, Smith LC. 2001. Gene therapy for the treatment of hemophilia B using PINC-formulated plasmid delivered to muscle with electroporation. Mol Ther 3:574–583. [PubMed][CrossRef]
43. Lee JS, Lee M, Kim SW. 2004. A new potent hFIX plasmid for hemophilia B gene therapy. Pharm Res 21:1229–1232. [PubMed][CrossRef]
44. Pringle IA, Hyde SC, Connolly MM, Lawton AE, Xu B, Nunez-Alonso G, Davies LA, Sumner-Jones SG, Gill DR. 2012. CpG-free plasmid expression cassettes for cystic fibrosis gene therapy. Biomaterials 33:6833–6842. [PubMed][CrossRef]
45. Bertoni C, Jarrahian S, Wheeler TM, Li Y, Olivares EC, Calos MP, Rando TA. 2006. Enhancement of plasmid-mediated gene therapy for muscular dystrophy by directed plasmid integration. Proc Natl Acad Sci USA 103:419–424. [PubMed][CrossRef]
46. Makinen K, Manninen H, Hedman M, Matsi P, Mussalo H, Alhava E, Ylä-Herttuala S. 2002. Increased vascularity detected by digital subtraction angiography after VEGF gene transfer to human lower limb artery: a randomized, placebo-controlled, double-blinded phase II study. Mol Ther 6:127–133. [PubMed][CrossRef]
47. Nikol S, Baumgartner I, Van Belle E, Diehm C, Visoná A, Capogrossi MC, Ferreira-Maldent N, Gallino A, Wyatt MG, Wijesinghe LD, Fusari M, Stephan D, Emmerich J, Pompilio G, Vermassen F, Pham E, Grek V, Coleman M, Meyer F. 2008. Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia. Mol Ther 16:972–978. [PubMed][CrossRef]
48. Vera Janavel G, Crottogini A, Cabeza Meckert P, Cuniberti L, Mele A, Papouchado M, Fernández N, Bercovich A, Criscuolo M, Melo C, Laguens R. 2006. Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep. Gene Ther 13:1133–1142. [PubMed][CrossRef]
49. Lu Q, Yao Y, Yao Y, Liu S, Huang Y, Lu S, Bai Y, Zhou B, Xu Y, Li L, Wang N, Wang L, Zhang J, Cheng X, Qin G, Ma W, Xu C, Tu X, Wang Q. 2012. Angiogenic factor AGGF1 promotes therapeutic angiogenesis in a mouse limb ischemia model. PLoS One 7:e46998. doi:10.1371/journal.pone.0046998. [CrossRef]
50. Xu L, Pirollo KF, Chang EH. 2001. Tumor-targeted p53-gene therapy enhances the efficacy of conventional chemo/radiotherapy. J Control Release 74:115–128. [PubMed][CrossRef]
51. Xu L, Huang CC, Huang W, Tang WH, Rait A, Yin YZ, Cruz I, Xiang LM, Pirollo KF, Chang EH. 2002. Systemic tumor-targeted gene delivery by anti-transferrin receptor scFv-immunoliposomes. Mol Cancer Ther 1:337–346. [PubMed]
52. Kim CK, Choi EJ, Choi SH, Park JS, Haider KH, Ahn WS. 2003. Enhanced p53 gene transfer to human ovarian cancer cells using the cationic nonviral vector, DDC. Gynecol Oncol 90:265–272. [PubMed][CrossRef]
53. Nakase M, Inui M, Okumura K, Kamei T, Nakamura S, Tagawa T. 2005. p53 gene therapy of human osteosarcoma using a transferrin-modified cationic liposome. Mol Cancer Ther 4:625–631. [PubMed][CrossRef]
54. Bil J, Wlodarski P, Winiarska M, Kurzaj Z, Issat T, Jozkowicz A, Wegiel B, Dulak J, Golab J. 2010. Photodynamic therapy-driven induction of suicide cytosine deaminase gene. Cancer Lett 290:216–222. [PubMed][CrossRef]
55. 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 EBV-based plasmid vector coupled with polyamidoamine dendrimer. Gene Ther 7:53–60. [PubMed][CrossRef]
56. Kendall RL, Thomas KA. 1993. Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci USA 90:10705–10709. [PubMed][CrossRef]
57. Fewell JG, Matar MM, Rice JS, Brunhoeber E, Slobodkin G, Pence C, Worker M, Lewis DH, Anwer K. 2009. Treatment of disseminated ovarian cancer using nonviral interleukin-12 gene therapy delivered intraperitoneally. J Gene Med 11:718–728. [PubMed][CrossRef]
58. Roos AK, King A, Pisa P. 2008. DNA vaccination for prostate cancer. Methods Mol Biol 423:463–472. [PubMed][CrossRef]
59. Wolchok JD, Yuan J, Houghton AN, Gallardo HF, Rasalan TS, Wang J, Zhang Y, Ranganathan R, Chapman PB, Krown SE, Livingston PO, Heywood M, Riviere I, Panageas KS, Terzulli SL, Perales MA. 2007. Safety and immunogenicity of tyrosinase DNA vaccines in patients with melanoma. Mol Ther 5:2044–2050. [PubMed][CrossRef]
60. Condon C, Watkins SC, Celluzzi CM, Thompson K, Falo LD. 1996. DNA-based immunization by in vivo transfection of dendritic cells. Nature Med 2:1122–1128. [PubMed][CrossRef]
61. Daud AI, DeConti RC, Andrews S, Urbas P, Riker AI, Sondak VK, Munster PN, Sullivan DM, Ugen KE, Messina JL, Heller R. 2008. Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. J Clinic Oncol 26:5896–5903. [PubMed]
62. Heinzerling L, Burg G, Dummer R, Maier T, Oberholzer PA, Schultz J, Elzaouk L, Pavlovic J, Moelling K. 2005. Intratumoral injection of DNA encoding human interleukin 12 into patients with metastatic melanoma: clinical efficacy. Human Gene Ther 16:35–48. [PubMed][CrossRef]
63. Tuszynski MH, Thal L, Pay M, Salmon DP, U HS, Bakay R, Patel P, Blesch A, Vahlsing HL, Ho G, Tong G, Potkin SG, Fallon J, Hansen L, Mufson EJ, Kordower JH, Gall C, Conner J. 2005. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nature Med 11:551–555. [PubMed][CrossRef]
64. Fernandes JC, Wang H, Jreyssaty C, Benderdour M, Lavigne P, Qiu X, Winnik FM, Zhang X, Dai K, Shi Q. 2008. Bone-protective effects of nonviral gene therapy with folate-chitosan DNA nanoparticle containing interleukin-1 receptor antagonist gene in rats with adjuvant-induced arthritis. Mol Ther 16:1243–1251. [PubMed][CrossRef]
65. Steinstraesser L, Hirsch T, Beller J, Mittler D, Sorkin M, Pazdierny G, Jacobsen F, Eriksson E, Steinau HU. 2007. Transient non-viral cutaneous gene delivery in burn wounds. J Gene Med 9:949–955. [PubMed][CrossRef]
66. Liu C, Fan M, Bian Z, Chen Z, Li Y. 2008. Effects of targeted fusion anti-caries DNA vaccine pGJA-P/VAX in rats with caries. Vaccine 26:6685–6689. [PubMed][CrossRef]
67. Ishikawa H, Takano M, Matsumoto N, Sawada H, Ide C, Mimura O. 2005. Effect of GDNF gene transfer into axotomized retinal ganglion cells using in vivo electroporation with a contact lens-type electrode. Gene Ther 12:289–298. [PubMed][CrossRef]
68. Hayashi T, Hasegawa K, Sasaki Y, Mori T, Adachi C, Maeda K. 2007. Systemic administration of interleukin-4 expressing plasmid DNA delays the development of glomerulonephritis and prolongs survival in lupus-prone female NZB x NZW F1 mice. Nephrol Dial Transplant 22:3131–3138. [PubMed][CrossRef]
69. Tohyama S, Onodera S, Tohyama H, Yasuda K, Nishihira J, Mizue Y, Hamasaka A, Abe R, Koyama Y. 2008. A novel DNA vaccine-targeting macrophage migration inhibitory factor improves the survival of mice with sepsis. Gene Ther 15:1513–1522. [PubMed][CrossRef]
70. De Laporte L, Yang Y, Zelivyanskaya ML, Cummings BJ, Anderson AJ, Shea LD. 2009. Plasmid releasing multiple channel bridges for transgene expression after spinal cord injury. Mol Ther 17:318–326. [PubMed][CrossRef]
71. Ferraro B, Cruz YL, Coppola D, Heller R. 2009. Intradermal delivery of plasmid VEGF(165) by electroporation promotes wound healing. Mol Ther 17:651–657. [PubMed][CrossRef]
72. Dean HJ, Fuller D, Osorio JE. 2003. Powder and particle-mediated approaches for delivery of DNA and protein vaccines into the epidermis. Comp Immunol Microbiol Infect Dis 26:373–388. [PubMed][CrossRef]
73. Uchijima M, Yoshida A, Nagata T, Koide Y. 1998. Optimization of codon usage of plasmid DNA vaccine is required for the effective MHC class I-restricted T cell responses against intracellular bacterium. J Immunol 161:5594–5599. [PubMed]
74. Babiuk S, Babiuk LA, van Drunen Littel-van den Hurk S. 2006. DNA vaccination: A simple concept with challenges regarding implementation. Int Rev Immunol 25:51–81. [PubMed][CrossRef]
75. Eo SK, Lee S, Chun S, Rouse BT. 2001. Modulation of immunity against herpes simplex virus infection via mucosal genetic transfer of plasmid DNA encoding chemokines. J Virol 75:569–578. [PubMed][CrossRef]
76. Leifert JA, Rodriguez-Carreno MP, Rodriguez F, Whitton JL. 2004. Targeting plasmid-encoded proteins to the antigen presentation pathways. Immunol Rev 199:40–53. [PubMed][CrossRef]
77. Vaine M, Wang S, Hackett A, Arthos J, Lu S. 2010. Antibody responses elicited through homologous or heterologous prime-boost DNA and protein vaccinations differ in functional activity and avidity. Vaccine 28:2999–3007. [PubMed][CrossRef]
78. Yager EJ, Dean HJ, Fuller DH. 2009. Prospects for developing an effective particle-mediated DNA vaccine against influenza. Expert Rev Vaccines 8:1205–1220. [PubMed][CrossRef]
79. Imoto J, Konishi E. 2007. Dengue tetravalent DNA vaccine increases its immunogenicity in mice when mixed with a dengue type 2 subunit vaccine or an inactivated Japanese encephalitis vaccine. Vaccine 25:1076–1084. [PubMed][CrossRef]
80. Yan J, Harris K, Khan AS, Draghia-Akli R, Sewell D, Weiner DB. 2008. Cellular immunity induced by a novel HPV18 DNA vaccine encoding an E6/E7 fusion consensus protein in mice and rhesus macaques. Vaccine 26:5210–5215. [PubMed][CrossRef]
81. Jones S, Evans K, McElwaine-Johnn H, Sharpe M, Oxford J, Lambkin-Williams R, Mant T, Nolan A, Zambon M, Ellis J, Beadle J, Loudon PT. 2009. DNA vaccination protects against an influenza challenge in a double-blind randomized placebo-controlled phase 1b clinical trial. Vaccine 27:2506–2512. [PubMed][CrossRef]
82. Silva MS, Prazeres DMF, Lança A, Atouguia J, Monteiro GA. 2009. Trans-sialidase from Trypanosoma brucei as a potential target for DNA vaccine development against African trypanosomiasis. Parasitol Res 105:1223–1229. [PubMed][CrossRef]
83. Wang QM, Kang L, Wang XH. 2009. Improved cellular immune response elicited by a ubiquitin-fused ESAT-6 DNA vaccine against Mycobacterium tuberculosis. Microbiol Immunol 53:384–390. [PubMed][CrossRef]
84. Prazeres DMF. 2011. Structure, p 85–128. In Plasmid Biopharmaceuticals: Basics Applications and Manufacturing. John Wiley & Sons, Inc., Hoboken, NJ. [CrossRef]
85. Faurez F, Dory D, Le Moigne V, Gravier R, Jestin A. 2010. Biosafety of DNA vaccines: New generation of DNA vectors and current knowledge on the fate of plasmids after injection. Vaccine 28:3888–3895. [PubMed][CrossRef]
86. Lechardeur D, Sohn KJ, Haardt M, Joshi PB, Monck M, Graham RW, Beatty B, Squire J, O'Brodovich H, Lukacs GL. 1999. Metabolic instability of plasmid DNA in the cytosol: a potential barrier to gene transfer. Gene Ther 6:482–497. [PubMed][CrossRef]
87. Ribeiro SC, Monteiro GA, Prazeres DMF. 2004. The role of polyadenylation signal secondary structures on the resistance of plasmid vectors to nucleases. J Gene Med 6:565–573. [PubMed][CrossRef]
88. Azzoni AR, Ribeiro SC, Monteiro GA, Prazeres DMF. 2007. The impact of polyadenylation signals on plasmid nuclease-resistance and transgene expression. J Gene Med 9:392–402. [PubMed][CrossRef]
89. Walther W, Stein U, Siegel R, Fichtner I, Schlag PM. 2005. Use of the nuclease inhibitor aurintricarboxylic acid (ATA) for improved non-viral intratumoral in vivo gene transfer by jet-injection. J Gene Med 7:477–485. [PubMed][CrossRef]
90. Ross GF, Bruno MD, Uyeda M, Suzuki K, Nagao K, Whitsett JA, Korfhagen TR. 1998. Enhanced reporter gene expression in cells transfected in the presence of DMI-2, an acid nuclease inhibitor. Gene Ther 5:1244–1250. [PubMed][CrossRef]
91. Prather KL, Edmonds MC, Herod JW. 2006. Identification and characterization of IS1 transposition in plasmid amplification mutants of E. coli clones producing DNA vaccines. Appl Microbiol Biotechnol 73:815–826. [PubMed][CrossRef]
92. Ribeiro SC, Oliveira PH, Prazeres DMF, Monteiro GA. 2008. High frequency plasmid recombination mediated by 28 bp direct repeats. Mol Biotechnol 40:252–260. [PubMed][CrossRef]
93. Oliveira PH, Prather KJ, Prazeres DMF, Monteiro GA. 2009. Structural instability of plasmid biopharmaceuticals: challenges and implications. Trends Biotechnol 27:503–511. [PubMed][CrossRef]
94. Oliveira PH, Prazeres DMF, Monteiro GA. 2009. Deletion formation mutations in plasmid expression vectors are unfavored by runaway amplification conditions and differentially selected under kanamycin stress. J Biotechnol 143:231–238. [PubMed][CrossRef]
95. Ritter T, Brandt C, Prösch S, Vergopoulos A, Vogt K, Kolls J, Volk HD. 2000. Stimulatory and inhibitory action of cytokines on the regulation of hCMV-IE promoter activity in human endothelial cells. Cytokine 12:1163–1170. [PubMed][CrossRef]
96. Rodova M, Jayini R, Singasani R, Chipps E, Islam MR. 2013. CMV promoter is repressed by p53 and activated by JNK pathway. Plasmid 69:223–230. [PubMed][CrossRef]
97. Yew NS, Przybylska M, Ziegler RJ, Liu D, Cheng SH. 2001. High and sustained transgene expression in vivo from plasmid vectors containing a hybrid ubiquitin promoter. Mol Ther 4:75–82. [PubMed][CrossRef]
98. Kutzler MA, Weiner DB. 2008. DNA vaccines: ready for prime time? Nat Rev Genet 9:776–788. [PubMed][CrossRef]
99. Williams JA, Carnes AE, Hodgson CP. 2009. Plasmid DNA vaccine vector design: Impact on efficacy, safety and upstream production. Biotechnol Adv 27:353–370. [PubMed][CrossRef]
100. Takeuchi O, Akira S. 2010. Pattern recognition receptors and inflammation. Cell 140:805–820. [PubMed][CrossRef]
101. Kawai T, Akira S. 2010. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11:373–384. [PubMed][CrossRef]
102. Barber GN. 2011. Innate immune DNA sensing pathways: STING, AIMII and the regulation of interferon production and inflammatory responses. Curr Opin Immunol 23:10–20. [PubMed][CrossRef]
103. Abe T, Harashima A, Xia T, Konno H, Konno K, Morales A, Ahn J, Gutman D, Barber GN. 2013. STING recognition of cytoplasmic DNA instigates cellular defense. Mol Cell 50:5–15. [PubMed][CrossRef]
104. Ishikawa H, Barber GN. 2011. The STING pathway and regulation of innate immune signaling in response to DNA pathogens. Cell Mol Life Sci 68:1157–1165. [PubMed][CrossRef]
105. Bode C, Zhao G, Steinhagen F, Kinjo T, Klinman DM. 2011. CpG DNA as a vaccine adjuvant. Expert Rev Vaccines 10:499–511. [PubMed][CrossRef]
106. Krieg AM. 1999. Direct immunologic activities of CpG DNA and implications for gene therapy. J Gene Med 1:56–63. [PubMed][CrossRef]
107. Gürsel M, Verthelyi D, Gürsel I, Ishii KJ, Klinman DM. 2002. Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide. J Leukoc Biol 71:813–820. [PubMed]
108. Rutz M, Metzger J, Gellert T, Luppa P, Lipford GB, Wagner H, Bauer S. 2004. Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner. Eur J Immunol 34:2541–2550. [PubMed][CrossRef]
109. Klinman DM. 2006. Adjuvant activity of CpG oligodeoxynucleotides. Int Rev Immunol 25:135–154. [PubMed][CrossRef]
110. Krieg AM. 2012. CpG still rocks! Update on an accidental drug. Nucleic Acid Ther 22:77-89. [PubMed]
111. Sørensen SJ, Bailey M, Hansen LH, Kroer N, Wuertz S. 2005. Studying plasmid horizontal transfer in situ: a critical review. Nat Rev Microbiol 3:700–710. [PubMed][CrossRef]
112. Oliveira PH, Mairhofer J. 2013. Marker-free plasmids for biotechnological applications – implications and perspectives. Trends Biotechnol 31:539–547. [PubMed][CrossRef]
113. Li L, Saade F, Petrovsky N. 2012. The future of human DNA vaccines. J Biotechnol 162:171–182. [PubMed][CrossRef]
114. Luke J, Carnes AE, Hodgson CP, Williams JA. 2009. Improved antibiotic-free DNA vaccine vectors utilizing a novel RNA based plasmid selection system. Vaccine 27:6454–6459. [PubMed][CrossRef]
115. Mairhofer J, Cserjan-Puschmann M, Striedner G, Nöbauer K, Razzazi-Fazeli E, Grabherr R. 2010. Marker-free plasmids for gene therapeutic applications–lack of antibiotic resistance gene substantially improves the manufacturing process. J Biotechnol 146:130–137. [PubMed][CrossRef]
116. Williams SG, Cranenburgh RM, Weiss AM, Wrighton CJ, Sherratt DJ, Hanak JA. 1998. Repressor titration: a novel system for selection and stable maintenance of recombinant plasmids. Nucleic Acids Res 26:2120–2124. [PubMed][CrossRef]
117. Kandimalla ER, Bhagat L, Wang D, Yu D, Sullivan T, La Monica N, Agrawal S. 2013. Design, synthesis and biological evaluation of novel antagonist compounds of Toll-like receptors 7, 8 and 9. Nucleic Acids Res 41:3947–3961. [PubMed][CrossRef]
118. Reyes-Sandoval A, Ertl HCJ. 2004. CpG methylation of a plasmid vector results in extended transgene product expression by circumventing induction of immune responses. Mol Ther 9:249–261. [PubMed][CrossRef]
119. Hyde SC, Pringle IA, Abdullah S, Lawton AE, Davies L, Varathalingam A, Nunez-Alonso G, Green AM, Bazzani RP, Sumner-Jones SG, Chan M, Li H, Yew NS, Cheng SH, Boyd AC, Davies JC, Griesenbach U, Porteous DJ, Sheppard DN, Munkonge FM, Alton EW, Gill DR. 2008. CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression. Nat Biotechnol 26:549–551. [PubMed][CrossRef]
120. Wolff JA, Ludtke JJ, Acsadi G, Williams P, Jani A. 1992. Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum Mol Genet 1:363–369. [PubMed][CrossRef]
121. Chen ZY, Riu E, He CY, Xu H, Kay MA. 2008. Silencing of episomal transgene expression in liver by plasmid bacterial backbone DNA is independent of CpG methylation. Mol Ther 16:548–556. [PubMed][CrossRef]
122. Lu J, Zhang F, Xu S, Fire AZ, Kay MA. 2012. The extragenic spacer length between the 5′ and 3′ ends of the transgene expression cassette affects transgene silencing from plasmid-based vectors. Mol Ther 20:2111–2119. [PubMed][CrossRef]
123. Suzuki M, Kasai K, Saeki Y. 2006. Plasmid DNA sequences present in conventional herpes simplex virus amplicon vectors cause rapid transgene silencing by forming inactive chromatin. J Virol 80:3293–3300. [PubMed][CrossRef]
124. Riu E, Chen ZY, Xu H, He CY, Kay MA. 2007. Histone modifications are associated with the persistence or silencing of vector-mediated transgene expression in vivo. Mol Ther 15:1348–1355. [PubMed][CrossRef]
125. Gracey Maniar LE, Maniar JM, Chen ZY, Lu J, Fire AZ, Kay MA. 2013. Minicircle DNA vectors achieve sustained expression reflected by active chromatin and transcriptional level. Mol Ther 21:131–138. [PubMed][CrossRef]
126. Argyros O, Wong SP, Fedonidis C, Tolmachov O, Waddington SN, Howe SJ, Niceta M, Coutelle C, Harbottle RP. 2011. Development of S/MAR minicircles for enhanced and persistent transgene expression in the mouse liver. J Mol Med 89:515–529. [PubMed][CrossRef]
127. Mayrhofer P, Blaesen M, Schleef M, Jechlinger W. 2008. Minicircle-DNA production by site specific recombination and protein-DNA interaction chromatography. J Gene Med 10:1253–1269. [PubMed][CrossRef]
128. Schakowski F, Gorschlüter M, Junghans C, Schroff M, Buttgereit P, Ziske C, Schöttker B, König-Merediz SA, Sauerbruch T, Wittig B, Schmidt-Wolf IG. 2001. A novel minimal-size vector (MIDGE) improves transgene expression in colon carcinoma cells and avoids transfection of undesired DNA. Mol Ther 3:793–800. [PubMed][CrossRef]
129. Schakowski F, Gorschlüter M, Buttgereit P, Märten A, Lilienfeld-Toal MV, Junghans C, Schroff M, König-Merediz SA, Ziske C, Strehl J, Sauerbruch T, Wittig B, Schmidt-Wolf IG. 2007. Minimal size MIDGE vectors improve transgene expression in vivo. In Vivo 21:17–23. [PubMed]
130. Prazeres DMF. 2011. Delivery, p 167–210. In Plasmid Biopharmaceuticals: Basics Applications and Manufacturing. John Wiley & Sons, Inc., Hoboken, NJ. [CrossRef]
131. Nishikawa M, Huang L. 2001. Nonviral vectors in the new millennium: delivery barriers in gene transfer. Hum Gene Ther 12:861–870. [PubMed][CrossRef]
132. Grigsby CL, Leong KW. 2010. Balancing protection and release of DNA: tools to address a bottleneck of non-viral gene delivery. J R Soc Interface 7:S67–S82. [PubMed][CrossRef]
133. Mahvi DM, Henry MB, Albertini MR, Weber S, Meredith K, Schalch H, Rakhmilevich A, Hank J, Sondel P. 2007. Intratumoral injection of IL-12 plasmid DNA--results of a phase I/IB clinical trial. Cancer Gene Ther 14:717–723. [PubMed][CrossRef]
134. Konstan MW, Davis PB, Wagener JS, Hilliard KA, Stern RC, Milgram LJ, Kowalczyk TH, Hyatt SL, Fink TL, Gedeon CR, Oette SM, Payne JM, Muhammad O, Ziady AG, Moen RC, Cooper MJ. 2004. Compacted DNA nanoparticles administered to the nasal mucosa of cystic fibrosis subjects are safe and demonstrate partial to complete cystic fibrosis transmembrane regulator reconstitution. Hum Gene Ther 15:1255–1269. [PubMed][CrossRef]
135. Wolff JA, Budker V. 2005. The mechanism of naked DNA uptake and expression. Adv Genet 54:3–20. [PubMed][CrossRef]
136. Satkauskas S, Bureau MF, Mahfoudi A, Mir LM. 2001. Slow accumulation of plasmid in muscle cells: supporting evidence for a mechanism of DNA uptake by receptor-mediated endocytosis. Mol Ther 4:317–323. [PubMed][CrossRef]
137. Budker V, Budker T, Zhang G, Subbotin VM, Loomis A, Wolff JA. 2000. Hypothesis: naked plasmid DNA is taken up by cells in vivo by a receptor-mediated process. J Gene Med 2:76–88. [PubMed][CrossRef]
138. Vaughan EE, DeGiulio JV, Dean DA. 2006. Intracellular trafficking of plasmids for gene therapy: mechanisms of cytoplasmic movement and nuclear import. Curr Gene Ther 6:671–681. [PubMed][CrossRef]
139. Dean DA, Strong DD, Zimmer WE. 2005. Nuclear entry of nonviral vectors. Gene Ther 12:881–890. [PubMed][CrossRef]
140. van der Aa MA, Mastrobattista E, Oosting RS, Hennink WE, Koning GA, Crommelin DJ. 2006. The nuclear pore complex: the gateway to successful nonviral gene delivery. Pharm Res 23:447–459. [PubMed][CrossRef]
141. Villemejane J, Mir LM. 2009. Physical methods of nucleic acid transfer: general concepts and applications. Br J Pharmacol 157:207–219. [PubMed][CrossRef]
142. Suda T, Suda K, Liu D. 2008. Computer-assisted hydrodynamic gene delivery. Mol Ther 16:1098–1104. [PubMed][CrossRef]
143. Mitragotri S. 2006. Current status and future prospects of needle-free liquid jet injectors. Nat Rev Drug Discov 5:543–548. [PubMed]
144. Wang S, Joshi S, Lu S. 2004. Delivery of DNA to skin by particle bombardment. Meth Mol Biol 245:185–193. [PubMed]
145. Dean HJ, Haynes J, Schmaljohn C. 2005. The role of particle-mediated DNA vaccines in biodefense preparedness. Adv Drug Deliv Rev 57:1315–1342. [PubMed][CrossRef]
146. Fuller DH, Loudon P, Schmaljohn C. 2006. Preclinical and clinical progress of particle-mediated DNA vaccines for infectious diseases. Methods 40:86–97. [PubMed][CrossRef]
147. Escoffre JM, Portet T, Wasungu L, Teissie J, Dean D, Rols MP. 2009. What is (still not) known of the mechanism by which electroporation mediates gene transfer and expression in cells and tissues. Mol Biotechnol 41:286–295. [PubMed][CrossRef]
148. Denet AR, Vanbever R, Preat V. 2004. Skin electroporation for transdermal and topical delivery. Adv Drug Deliv Rev 56:659–674. [PubMed][CrossRef]
149. Chiarella P, Massi E, De Robertis M, Sibilio A, Parrella P, Fazio VM, Signori E. 2008. Electroporation of skeletal muscle induces danger signal release and antigen-presenting cell recruitment independently of DNA vaccine administration. Expert Opin Biol Ther 8:1645–1657. [PubMed][CrossRef]
150. Faurie C, Rebersek M, Golzio M, Kanduser M, Escoffre JM, Pavlin M, Teissie J, Miklavcic D, Rols MP. 2010. Electro-mediated gene transfer and expression are controlled by the life-time of DNA/membrane complex formation. J Gene Med 12:117–125. [PubMed][CrossRef]
151. Luxembourg A, Hannaman D, Ellefsen B, Nakamura G, Bernard R. 2006. Enhancement of immune responses to an HBV DNA vaccine by electroporation. Vaccine 24:4490–4493. [PubMed][CrossRef]
152. Luxembourg A, Evans CF, Hannaman D. 2007. Electroporation-based DNA immunisation: translation to the clinic. Expert Opin Biol Ther 7:1647–1664. [PubMed][CrossRef]
153. Heller LC, Heller R. 2006. In vivo electroporation for gene therapy. Hum Gene Ther 17:890–897. [PubMed][CrossRef]
154. Bodles-Brakhop AM, Heller R, Draghia-Akli R. 2009. Electroporation for the delivery of DNA-based vaccines and immunotherapeutics: current clinical developments. Mol Ther 17:585–592. [PubMed][CrossRef]
155. Templeton NS, Lasic DD, Frederik PM, Strey HH, Roberts DD, Pavlakis GN. 1997. Improved DNA: liposome complexes for increased systemic delivery and gene expression. Nat Biotechnol 15:647–652. [PubMed][CrossRef]
156. Farrell LL, Pepin J, Kucharski C, Lin X, Xu Z, Uludag H. 2007. A comparison of the effectiveness of cationic polymers poly-L-lysine (PLL) and polyethylenimine (PEI) for non-viral delivery of plasmid DNA to bone marrow stromal cells (BMSC). Eur J Pharm Biopharm 65:388–397. [PubMed][CrossRef]
157. Aral C, Akbuga J. 2003. Preparation and in vitro transfection efficiency of chitosan microspheres containing plasmid DNA:poly(L-lysine) complexes. J Pharm Pharm Sci 6:321–326. [PubMed]
158. Basarkar A, Devineni D, Palaniappan R, Singh J. 2007. Preparation, characterization, cytotoxicity and transfection efficiency of poly(DL-lactide-co-glycolide) and poly(DL-lactic acid) cationic nanoparticles for controlled delivery of plasmid DNA. Int J Pharm 343:247–254. [PubMed][CrossRef]
159. Mok H, Park TG. 2008. Direct plasmid DNA encapsulation within PLGA nanospheres by single oil-in-water emulsion method. Eur J Pharm Biopharm 68:105–111. [PubMed][CrossRef]
160. Hao T, McKeever U, Hedley ML. 2000. Biological potency of microsphere encapsulated plasmid DNA. J Control Release 69:249–259. [PubMed][CrossRef]
161. Singh M, Briones M, Ott G, O'Hagan D. 2000. Cationic microparticles: a potent delivery system for DNA vaccines. Proc Natl Acad Sci USA 97:811–816. [PubMed][CrossRef]
162. Luo Y, O'Hagan D, Zhou H, Singh M, Ulmer J, Reisfeld RA, James Primus F, Xiang R. 2003. Plasmid DNA encoding human carcinoembryonic antigen (CEA) adsorbed onto cationic microparticles induces protective immunity against colon cancer in CEA-transgenic mice. Vaccine 21:1938–1947. [PubMed][CrossRef]
163. He X, Jiang L, Wang F, Xiao Z, Li J, Liu LS, Li D, Ren D, Jin X, Li K, He Y, Shi K, Guo Y, Zhang Y, Sun S. 2005. Augmented humoral and cellular immune responses to hepatitis B DNA vaccine adsorbed onto cationic microparticles. J Control Release 107:357–372. [PubMed][CrossRef]
164. Mollenkopf HJ, Dietrich G, Fensterle J, Grode L, Diehl KD, Knapp B, Singh M, O'Hagan DT, Ulmer JB, Kaufmann SH. 2004. Enhanced protective efficacy of a tuberculosis DNA vaccine by adsorption onto cationic PLG microparticles. Vaccine 22:2690–2695. [PubMed][CrossRef]
165. Bozkir A, Saka OM. 2004. Chitosan nanoparticles for plasmid DNA delivery: effect of chitosan molecular structure on formulation and release characteristics. Drug Deliv 11:2690–2695. [PubMed][CrossRef]
166. Wang C-Q, Wu J-L, Zhuo R-X, Cheng S-X. 2014. Protamine sulfate–calcium carbonate–plasmid DNA ternary nanoparticles for efficient gene delivery. Mol BioSyst 10:672–678. [PubMed][CrossRef]
167. Nichols WW, Ledwith BJ, Manam SV, Troilo PJ. 1995. Potential DNA vaccine integration into host cell genome. Ann N Y Acad Sci 772:30–39. [PubMed][CrossRef]
168. Mor G, Singla M, Steinberg AD, Hoffman SL, Okuda K, Klinman DM. 1997. Do DNA vaccines induce autoimmune disease? Hum Gene Ther 8:293–300. [PubMed][CrossRef]
169. European Agency for the Evaluation Medicinal Products. 24 April 2001. Note for guidance on quality, preclinical and clinical aspects of gene transfer medicinal products (CPMP/BWP/3088/99). European Medicines Agency, London, UK.
170. US Food and Drug Administration. 2007. Guidance for industry: considerations for plasmid DNA vaccines for preventive infectious disease indications. US Food and Drug Administration, Rockville, MD,
171. Cichutek K. 2000. DNA vaccines: development, standardization and regulation. Intervirology 43:331–338. [PubMed][CrossRef]
172. Ledwith BJ, Manam S, Troilo PJ, Barnum AB, Pauley CJ, Griffiths TG, Harper LB, Beare CM, Bagdon WJ, Nichols WW. 2000. Plasmid DNA vaccines: investigation of integration into host cellular DNA following intramuscular injection in mice. Intervirology 43:258–272. [PubMed][CrossRef]
173. Wang Z, Troilo PJ, Wang X, Griffiths TG, Pacchione SJ, Barnum AB, Harper LB, Pauley CJ, Niu Z, Denisova L, Follmer TT, Rizzuto G, Ciliberto G, Fattori E, Monica NL, Manam S, Ledwith BJ. 2004. Detection of integration of plasmid DNA into host genomic DNA following intramuscular injection and electroporation. Gene Ther 11:711–721. [PubMed][CrossRef]
174. Sheets RL, Stein J, Manetz TS, Duffy C, Nason M, Andrews C, Kong WP, Nabel GJ, Gomez PL. 2006. Biodistribution of DNA plasmid vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile virus is similar, without integration, despite differing plasmid backbones or gene inserts. Toxicol Sci 91:610–619. [PubMed][CrossRef]
175. Iiizumi S, Kurosawa A, So S, Ishii Y, Chikaraishi Y, Ishii A, Koyama H, Adachi N. 2008. Impact of non-homologous end-joining deficiency on random and targeted DNA integration: implications for gene targeting. Nucleic Acids Res 36:6333–6342. [PubMed][CrossRef]
176. Pilling AM, Harman RM, Jones SA, McCormack NA, Lavender D, Haworth R. 2002. The assessment of local tolerance, acute toxicity, and DNA biodistribution following particle-mediated delivery of a DNA vaccine to minipigs. Toxicol Pathol 30:298–305. [PubMed][CrossRef]
177. Manam S, Ledwith BJ, Barnum AB, Troilo PJ, Pauley CJ, Harper LB, Griffiths TG, Niu Z, Denisova L, Follmer TT, Pacchione SJ, Wang Z, Beare CM, Bagdon WJ, Nichols WW. 2000. Plasmid DNA vaccines: tissue distribution and effects of DNA sequence, adjuvants and delivery method on integration into host DNA. Intervirology 43:273–281. [PubMed][CrossRef]
178. Nabel EG, Gordon D, Yang ZY, Xu L, San H, Plautz GE, Wu BY, Gao X, Huang L, Nabel GJ. 1992. Gene transfer in vivo with DNA-liposome complexes: lack of autoimmunity and gonadal localization. Hum Gene Ther 3:649–656. [PubMed][CrossRef]
179. Mor G, Eliza M. 2001. Plasmid DNA vaccines. Immunology, tolerance, and autoimmunity. Mol Biotechnol 19:245–250. [PubMed][CrossRef]
180. Choi SM, Lee DS, Son MK, Sohn YS, Kang KK, Kim CY, Kim BM, Kim WB. 2003. Safety evaluation of GX-12. A new DNA vaccine for HIV infection in rodents. Drug Chem Toxicol 26:271–284. [PubMed][CrossRef]
181. Schalk JAC, Mooi FR, Berbers GAM, van Aerts LAGJM, Ovelgönne H, Kimman TG. 2006. Preclinical and clinical safety studies on DNA vaccines. Hum Vaccines 2:45–53. [PubMed][CrossRef]
182. Sheets RL, Stein J, Manetz TS, Andrews C, Bailer R, Rathmann J, Gomez PL. 2006. Toxicological safety evaluation of DNA plasmid vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile virus is similar despite differing plasmid backbones or gene-inserts. Toxicol Sci 91:620–630. [PubMed][CrossRef]
183. Tavel JA, Martin JE, Kelly GG, Enama ME, Shen JM, Gomez PL, Andrews CA, Koup RA, Bailer RT, Stein JA, Roederer M, Nabel GJ, Graham BS. 2007. Safety and immunogenicity of a Gag-Pol candidate HIV-1 DNA vaccine administered by a needle-free device in HIV-1-seronegative subjects. J Acquir Immune Defic Syndr 44:601–605. [PubMed][CrossRef]
184. Prazeres DMF. 2011. Product and process development, p 69–84. In Plasmid Biopharmaceuticals: Basics Applications and Manufacturing. John Wiley & Sons, Inc., Hoboken, NJ. [CrossRef]
185. Gonçalves GAL, Prazeres DMF, Monteiro GA, Prather KLJ. 2013. De Novo Creation of MG1655-derived Escherichia coli strains specifically designed for plasmid DNA production. App Microbiol Biotechnol 97:611–620. [PubMed][CrossRef]
186. Carnes AE, Williams JA. 2007. Plasmid DNA manufacturing technology. Recent Pat Biotechnol 1:151–166. [PubMed][CrossRef]
187. Listner K, Bentley L, Okonkowski J, Kistler C, Wnek R, Caparoni A, Junker B, Robinson D, Salmon P, Chartrain M. 2006. Development of a highly productive and scalable plasmid DNA production platform. Biotechnol Prog 22:1335–1345. [PubMed][CrossRef]
188. Freitas SS, Santos JAL, Prazeres DMF. 2006. Optimisation of isopropanol and ammonium sulphate precipitation steps in the purification of plasmid DNA. Biotechnol Prog 22:1179–1186. [PubMed][CrossRef]
189. Gomes GA, Azevedo AM, Aires-Barros MR, Prazeres DMF. 2010. Clearance of host-cell impurities from plasmid-containing lysates by boronate adsorption. J Chromatogr A 1217:2262–2266. [PubMed][CrossRef]
190. Gomes GA, Azevedo AM, Aires-Barros MR, Prazeres DMF. 2009. Purification of plasmid DNA using aqueous two-phase systems with PEG 600 and sodium citrate/ammonium sulphate. Sep Pur Technol 65:22–30. [CrossRef]
191. Freitas S, Santos JAL, Prazeres DMF. 2009. Plasmid purification by hydrophobic interaction chromatography using sodium citrate in the mobile phase. Sep Pur Technol 65:95–104. [CrossRef]
192. Sousa F, Freitas SS, Azzonni A, Prazeres DMF, Queiroz JA. 2006. Selective purification of supercoiled plasmid DNA from cell lysates with a single histidine-agarose chromatography step. Biotechnol App Biochem 45:131–140. [PubMed][CrossRef]
193. Lemmens R, Olsson U, Nyhammar T, Stadler J. 2003. Supercoiled plasmid DNA: selective purification by thiophilic/aromatic adsorption. J Chromatog B 784:291–300. [PubMed][CrossRef]
194. Diogo MM, Queiroz JA, Prazeres DMF. 2005. Chromatography of plasmid DNA. J Chrom A 1069:3–22. [PubMed][CrossRef]
195. Prazeres DMF. 2009. Chromatographic separation of plasmid DNA using macroporous beads, p 335–361. In Mattiasson B, Kumar A, Galaev IY (ed), Macroporous Polymers: Production, Properties and Biotechnological/Biomedical Applications. CRC Press, New York, NY. [CrossRef]
196. Urthaler J, Buchinger W, Necina R. 2005. Industrial scale cGMP purification of pharmaceutical-grade plasmid DNA. Chem Eng Technol 28:1408–1420. [CrossRef]
197. Watson MP, Winters MA, Sagar SL, Konz JO. 2006. Sterilizing filtration of plasmid DNA: effects of plasmid concentration, molecular weight, and conformation. Biotechnol Prog 22:465–470. [PubMed][CrossRef]
198. Prazeres DMF. 2011. Veterinary case studies: West Nile, infectious hematopoietic necrosis and melanoma, p 69–84. In Plasmid Biopharmaceuticals: Basics Applications and Manufacturing. John Wiley & Sons, Inc., Hoboken, NJ. [CrossRef]
199. Powell K. 2004. DNA vaccines—back in the saddle again? Nat Biotechnol 22:799–801. [PubMed][CrossRef]
200. Anonymous. 2008. West Nile-Innovator DNA—The first USDA approved DNA vaccine. Fort Dodge Animal Health, Fort Dodge, IA.
201. Novartis. 19 July 2005. Novel Novartis vaccine to protect Canadian salmon farms from devastating viral disease. Novartis Animal Health Inc., Basel, Switzerland.
202. Merial. 26 March 2007. USDA grants conditional approval for first therapeutic vaccine to treat cancer. Merial Limited, Duluth, GA.
203. Person R, Bodles-Brakhop AM, Pope MA, Brown PA, Khan AS, Draghia-Akli R. 2008. Growth hormone-releasing hormone plasmid treatment by electroporation decreases offspring mortality over three pregnancies. Mol Ther 16:1891–1897. [PubMed][CrossRef]
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/content/journal/microbiolspec/10.1128/microbiolspec.PLAS-0022-2014
2014-11-07
2017-09-23

Abstract:

Plasmids are currently an indispensable molecular tool in life science research and a central asset for the modern biotechnology industry, supporting its mission to produce pharmaceutical proteins, antibodies, vaccines, industrial enzymes, and molecular diagnostics, to name a few key products. Furthermore, plasmids have gradually stepped up in the past 20 years as useful biopharmaceuticals in the context of gene therapy and DNA vaccination interventions. This review provides a concise coverage of the scientific progress that has been made since the emergence of what are called today plasmid biopharmaceuticals. The most relevant topics are discussed to provide researchers with an updated overview of the field. A brief outline of the initial breakthroughs and innovations is followed by a discussion of the motivation behind the medical uses of plasmids in the context of therapeutic and prophylactic interventions. The molecular characteristics and rationale underlying the design of plasmid vectors as gene transfer agents are described and a description of the most important methods used to deliver plasmid biopharmaceuticals (gene gun, electroporation, cationic lipids and polymers, and micro- and nanoparticles) is provided. The major safety issues (integration and autoimmunity) surrounding the use of plasmid biopharmaceuticals is discussed next. Aspects related to the large-scale manufacturing are also covered, and reference is made to the plasmid products that have received marketing authorization as of today.

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Plasmid biopharmaceuticals: the formative years. doi:10.1128/microbiolspec.PLAS-0022-2014.f1

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.PLAS-0022-2014
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Basic physical characteristics of plasmid vectors. Data presented is for 2,000- to 10,000-bp plasmids with a typical degree of supercoiling (Prazeres, 2011). Image is reprinted with permission from reference 84 with permission from Wiley. Copyright 2011, John Wiley and Sons, Inc. doi:10.1128/microbiolspec.PLAS-0022-2014.f2

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.PLAS-0022-2014
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(A) Schematic representation of the recombination of a parental plasmid (PP) into a minicircle (MC) and a miniplasmid (MP) via the excision of the eukaryotic expression cassette that is flanked by two multimer resolution sites (MRS). (B) Agarose gel electrophoresis showing a parental plasmid before the induction of recombination (BR) and minicircle and miniplasmid species after recombination (AR). Abbreviations: ORI, origin of replication; GOI, gene of interest. doi:10.1128/microbiolspec.PLAS-0022-2014.f3

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.PLAS-0022-2014
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The intracellular barriers to plasmid-based gene transfer. In their journey to the nucleus, plasmids have to cross the phospholipidic cell membrane through endocytosis (1), escape entrapment and degradation in endosomes and lysosomes (2), survive degradation by cytosolic nucleases, traffic the overcrowded cytoplasm (3), and translocate across the nuclear envelope (4). doi:10.1128/microbiolspec.PLAS-0022-2014.f4

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.PLAS-0022-2014
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plasmid delivery. Plasmid DNA can be combined and formulated with buffers, stabilizers, and inorganic or organic matrices and molecules to produce: (i) a saline solution of plasmid, (ii) gold particles coated with plasmid, (iii) plasmids complexed with cationic lipids or polymers, (iv) polymeric microparticles with encapsulated or surface-adsorbed plasmid, or (v) nanoparticles of compacted plasmid. doi:10.1128/microbiolspec.PLAS-0022-2014.f5

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An overview of the different activities and steps involved in the manufacturing of plasmid biopharmaceuticals. doi:10.1128/microbiolspec.PLAS-0022-2014.f6

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.PLAS-0022-2014
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