Thromb Haemost 2009; 102(06): 1135-1143
DOI: 10.1160/TH09-10-0724
Theme Issue Article
Schattauer GmbH

Genetic manipulation of endothelial cells by viral vectors

Dirk Lindemann
1   Institute of Virology, Medizinische Fakultät “Carl Gustav Carus”, Technische Universität Dresden, Germany
2   CRTD, Center for Regenerative Therapies Dresden, Technische Universität Dresden, Germany
,
Hans Schnittler
2   CRTD, Center for Regenerative Therapies Dresden, Technische Universität Dresden, Germany
3   Institute of Anatomy and Cell Biology, Westfälische Wilhelms-Universität Münster, Münster, Germany
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 24. Oktober 2009

Accepted after minor revision: 08. November 2009

Publikationsdatum:
28. November 2017 (online)

Summary

The need for uncovering molecular mechanisms in endothelial cell biology has tremendously increased in the last decades as it became more and more clear that the endothelium is an important target in nearly all diseases and treatments (drug delivery) and plays a central role in regeneration processes. One of the critical methods generally applied in cell biology research to uncover structural and functional aspects is the modulation of protein expression by over-expression, expression of mutant variants or gene silencing. This strategy, however, requires genetic manipulation of the respective cells. The classical gene transfer by chemical transfection techniques works pretty well in a large variety of cultured cells but fails for most endothelial cell types. Insufficient transfection rates and gene expression levels as well as the sensitivity of the endothelium against chemical transfection reagents limits utilisation of this technique for endothelial cell biology research. This holds true not only for primary endothelial cell cultures and endothelial cells in vivo but also for endothelial cell lines, e.g. endothelioma cells. The development of viral vectors originally designed for gene therapy approaches has significantly improved the methodological spectrum in endothelial cell research. Two viral vector systems, based on retroviruses and adenoviruses, deliver transgenic information highly efficient into both cultured endothelial cells and in endothelial cells in vivo, respectively. This review aims to give a comprehensive overview of these two vector systems that appear to be reliable and efficient tools for gene delivery into endothelial cell types.

 
  • References

  • 1 Aird W. Endothelial Biomedicine. Cambridge University Press; 2007
  • 2 Waehler R, Russell SJ, Curiel DT. Engineering targeted viral vectors for gene therapy. Nat Rev Genet 2007; 08: 573-587.
  • 3 Graham FL, Smiley J, Russell WC. et al. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol 1977; 36: 59-74.
  • 4 Linial M, Fan H, Hahn B. et al. Retroviridae. In: Virus Taxonomy. 2nd ed. Elsevier Inc; Oxford: 2005: 421-440.
  • 5 Anderson WF, Blaese RM, Culver K. The ADA human gene therapy clinical protocol: Points to Consider response with clinical protocol, July 6, 1990. Hum Gene Ther 1990; 01: 331-362.
  • 6 Wei CM, Gibson M, Spear PG. et al. Construction and isolation of a transmissible retrovirus containing the src gene of Harvey murine sarcoma virus and the thymidine kinase gene of herpes simplex virus type 1. J Virol 1981; 39: 935-944.
  • 7 Cepko CL, Roberts BE, Mulligan RC. Construction and applications of a highly transmissible murine retrovirus shuttle vector. Cell 1984; 37: 1053-1062.
  • 8 Mann R, Mulligan RC, Baltimore D. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell 1983; 33: 153-159.
  • 9 Cavazzana-Calvo M, Hacein-Bey S, de Saint GBasile. et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 2000; 288: 669-672.
  • 10 Cavazzana-Calvo M, Thrasher A, Mavilio F. The future of gene therapy. Nature 2004; 427: 779-781.
  • 11 Roe T, Reynolds TC, Yu G. et al. Integration of murine leukemia virus DNA depends on mitosis. EMBO J 1993; 12: 2099-2108.
  • 12 Miller DG, Adam MA, Miller AD. Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol 1990; 10: 4239-4242.
  • 13 Kiefer F, Courtneidge SA, Wagner EF. Oncogenic properties of the middle T antigens of polyomaviruses. Adv Cancer Res 1994; 64: 125-157.
  • 14 Primo L, Roca C, Ferrandi C. et al. Human endothelial cells expressing polyoma middle T induce tumors. Oncogene 2000; 19: 3632-3641.
  • 15 Eton D, Terramani TT, Wang Y. et al. Genetic engineering of stent grafts with a highly efficient pseudotyped retroviral vector. J Vasc Surg 1999; 29: 863-873.
  • 16 Inaba M, Toninelli E, Vanmeter G. et al. Retroviral gene transfer: effects on endothelial cell phenotype. J Surg Res 1998; 78: 31-36.
  • 17 Zheng L, Dengler TJ, Kluger MS. et al. Cytoprotection of human umbilical vein endothelial cells against apoptosis and CTL-mediated lysis provided by caspase-resistant Bcl-2 without alterations in growth or activation responses. J Immunol 2000; 164: 4665-4671.
  • 18 Sanders DA. No false start for novel pseudotyped vectors. Curr Opin Biotechnol 2002; 13: 437-442.
  • 19 Emi N, Friedmann T, Yee JK. Pseudotype formation of murine leukemia virus with the G protein of vesicular stomatitis virus. J Virol 1991; 65: 1202-1207.
  • 20 Pear WS, Nolan GP, Scott ML. et al. Production of high-titer helper-free retroviruses by transient transfection. Proc Natl Acad Sci USA 1993; 90: 8392-8396.
  • 21 Soneoka Y, Cannon PM, Ramsdale EE. et al. A transient three-plasmid expression system for the production of high titer retroviral vectors. Nucleic Acids Res 1995; 23: 628-633.
  • 22 Batzlsperger CA, Achatz S, Spreng J. et al. Evidence for a possible inhibitory interaction between the HO-1/CO-and Akt/NO-pathways in human endothelial cells. Cardiovasc Drugs Ther 2007; 21: 347-355.
  • 23 Koren B, Weisz A, Fischer L. et al. Efficient transduction and seeding of human endothelial cells onto metallic stents using bicistronic pseudotyped retroviral vectors encoding vascular endothelial growth factor. Cardiovasc Revasc Med 2006; 07: 173-178.
  • 24 Liu L, Anderson WF, Beart RW. et al. Incorporation of tumor vasculature targeting motifs into moloney murine leukemia virus env escort proteins enhances retrovirus binding and transduction of human endothelial cells. J Virol 2000; 74: 5320-5328.
  • 25 Masood R, Gordon EM, Whitley MD. et al. Retroviral vectors bearing IgG-binding motifs for antibody-mediated targeting of vascular endothelial growth factor receptors. Int J Mol Med 2001; 08: 335-343.
  • 26 Naldini L, Blomer U, Gallay P. et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 1996; 272: 263-267.
  • 27 Vigna E, Naldini L. Lentiviral vectors: excellent tools for experimental gene transfer and promising candidates for gene therapy. J Gene Med 2000; 02: 308-316.
  • 28 Lewis P, Hensel M, Emerman M. Human immunodeficiency virus infection of cells arrested in the cell cycle. EMBO J 1992; 11: 3053-3058.
  • 29 Lewis PF, Emerman M. Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J Virol 1994; 68: 510-516.
  • 30 Shichinohe T, Bochner BH, Mizutani K. et al. Development of lentiviral vectors for antiangiogenic gene delivery. Cancer Gene Ther 2001; 08: 879-889.
  • 31 Follenzi A, Ailles LE, Bakovic S. et al. Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences. Nat Genet 2000; 25: 217-222.
  • 32 Cefai D, Simeoni E, Ludunge KM. et al. Multiply attenuated, self-inactivating lentiviral vectors efficiently transduce human coronary artery cells in vitro and rat arteries in vivo. J Mol Cell Cardiol 2005; 38: 333-344.
  • 33 De Palma M, Venneri MA, Naldini L. In vivo targeting of tumor endothelial cells by systemic delivery of lentiviral vectors. Hum Gene Ther 2003; 14: 1193-1206.
  • 34 Rethwilm A. Foamy virus vectors: an awaited alternative to gammaretro-and lentiviral vectors. Curr Gene Ther 2007; 07: 261-271.
  • 35 Vassilopoulos G, Rethwilm A. The usefulness of a perfect parasite. Gene Ther 2008; 15: 1299-1301.
  • 36 Lindemann D, Goepfert PA. The foamy virus envelope glycoproteins. Curr Top Microbiol Immunol 2003; 277: 111-129.
  • 37 Arnberg N. Adenovirus receptors: implications for tropism, treatment and targeting. Rev Med Virol 2009; 19: 165-178.
  • 38 Sharma A, Li X, Bangari DS. et al. Adenovirus receptors and their implications in gene delivery. Virus Res 2009; 143: 184-194.
  • 39 Vincent T, Pettersson RF, Crystal RG. et al. Cytokine-mediated downregulation of coxsackievirus-adenovirus receptor in endothelial cells. J Virol 2004; 78: 8047-8058.
  • 40 Meier O, Greber UF. Adenovirus endocytosis. J Gene Med 2004; 06 (Suppl. 01) S152-163.
  • 41 Gastaldelli M, Imelli N, Boucke K. et al. Infectious adenovirus type 2 transport through early but not late endosomes. Traffic 2008; 09: 2265-2278.
  • 42 Greber UF, Webster P, Weber J. et al. The role of the adenovirus protease on virus entry into cells. Embo J 1996; 15: 1766-1777.
  • 43 Campos SK, Barry MA. Current advances and future challenges in Adenoviral vector biology and targeting. Curr Gene Ther 2007; 07: 189-204.
  • 44 Fallaux FJ, Bout A, van der Velde I. et al. New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses. Hum Gene Ther 1998; 09: 1909-1917.
  • 45 Danthinne X, Imperiale MJ. Production of first generation adenovirus vectors: a review. Gene Ther 2000; 07: 1707-1714.
  • 46 Alba R, Bosch A, Chillon M. Gutless adenovirus: last-generation adenovirus for gene therapy. Gene Ther 2005; 12 (Suppl. 01) S18-27.
  • 47 McConnell MJ, Imperiale MJ. Biology of adenovirus and its use as a vector for gene therapy. Hum Gene Ther 2004; 15: 1022-1033.
  • 48 Mizuguchi H, Hayakawa T. Targeted adenovirus vectors. Hum Gene Ther 2004; 15: 1034-1044.
  • 49 Ogawara K, Kuldo JM, Oosterhuis K. et al. Functional inhibition of NF-kappaB signal transduction in alphavbeta3 integrin expressing endothelial cells by using RGD-PEG-modified adenovirus with a mutant IkappaB gene. Arthritis Res Ther 2006; 08: R32.
  • 50 Wang N, Verna L, Hardy S. et al. Adenovirus-mediated overexpression of c-Jun and c-Fos induces intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in human endothelial cells. Arterioscler Thromb Vasc Biol 1999; 19: 2078-2084.
  • 51 Wrighton CJ, Hofer-Warbinek R, Moll T. et al. Inhibition of endothelial cell activation by adenovirusmediated expression of I kappa B alpha, an inhibitor of the transcription factor NF-kappa B. J Exp Med 1996; 183: 1013-1022.
  • 52 Soares MP, Muniappan A, Kaczmarek E. et al. Adenovirus-mediated expression of a dominant negative mutant of p65/RelA inhibits proinflammatory gene expression in endothelial cells without sensitizing to apoptosis. J Immunol 1998; 161: 4572-4582.
  • 53 Erzurum SC, Lemarchand P, Rosenfeld MA. et al. Protection of human endothelial cells from oxidant injury by adenovirus-mediated transfer of the human catalase cDNA. Nucleic Acids Res 1993; 21: 1607-1612.
  • 54 Fennell JP, Brosnan MJ, Frater AJ. et al. Adenovirus-mediated overexpression of extracellular superoxide dismutase improves endothelial dysfunction in a rat model of hypertension. Gene Ther 2002; 09: 110-117.
  • 55 Lee KU, Lee IK, Han J. et al. Effects of recombinant adenovirus-mediated uncoupling protein 2 overexpression on endothelial function and apoptosis. Circ Res 2005; 96: 1200-1207.
  • 56 Lin SJ, Shyue SK, Liu PL. et al. Adenovirus-mediated overexpression of catalase attenuates oxLDL-induced apoptosis in human aortic endothelial cells via AP-1 and C-Jun N-terminal kinase/extracellular signal-regulated kinase mitogen-activated protein kinase pathways. J Mol Cell Cardiol 2004; 36: 129-139.
  • 57 Miller WH, Brosnan MJ, Graham D. et al. Targeting endothelial cells with adenovirus expressing nitric oxide synthase prevents elevation of blood pressure in stroke-prone spontaneously hypertensive rats. Mol Ther 2005; 12: 321-327.
  • 58 Ooboshi H, Chu Y, Rios CD. et al. Altered vascular function after adenovirus-mediated overexpression of endothelial nitric oxide synthase. Am J Physiol 1997; 273: H265-270.
  • 59 Ren J, Zhang X, Scott GI. et al. Adenovirus gene transfer of recombinant endothelial nitric oxide synthase enhances contractile function in ventricular myocytes. J Cardiovasc Pharmacol 2004; 43: 171-177.
  • 60 Yan J, Tang GL, Wang R. et al. Optimization of adenovirus-mediated endothelial nitric oxide synthase delivery in rat hindlimb ischemia. Gene Ther 2005; 12: 1640-1650.
  • 61 Baffi J, Byrnes G, Chan CC. et al. Choroidal neovascularization in the rat induced by adenovirus mediated expression of vascular endothelial growth factor. Invest Ophthalmol Vis Sci 2000; 41: 3582-3589.
  • 62 Kholova I, Koota S, Kaskenpaa N. et al. Adenovirus-mediated gene transfer of human vascular endothelial growth factor-d induces transient angiogenic effects in mouse hind limb muscle. Hum Gene Ther 2007; 18: 232-244.
  • 63 Roy H, Bhardwaj S, Babu M. et al. Adenovirus-mediated gene transfer of placental growth factor to perivascular tissue induces angiogenesis via upregulation of the expression of endogenous vascular endothelial growth factor-A. Hum Gene Ther 2005; 16: 1422-1428.
  • 64 Yu MJ, Shen WY, Lai MC. et al. Generation and characterization of a recombinant adenovirus expressing vascular endothelial growth factor for studies of neovascularization in the eye. Aust N Z J Ophthalmol 1999; 27: 250-253.
  • 65 Bertelmann E, Ritter T, Vogt K. et al. Efficiency of cytokine gene transfer in corneal endothelial cells and organ-cultured corneas mediated by liposomal vehicles and recombinant adenovirus. Ophthalmic Res 2003; 35: 117-124.
  • 66 Kang H, Yang PY, Rui YC. Adenovirus viral interleukin-10 inhibits adhesion molecule expressions induced by hypoxia/reoxygenation in cerebrovascular endothelial cells. Acta Pharmacol Sin 2008; 29: 50-56.
  • 67 Ivanciu L, Gerard RD, Tang H. et al. Adenovirusmediated expression of tissue factor pathway inhibitor-2 inhibits endothelial cell migration and angiogenesis. Arterioscler Thromb Vasc Biol 2007; 27: 310-316.
  • 68 Qiu K, Su Y, Block ER. Use of recombinant calpain-2 siRNA adenovirus to assess calpain-2 modulation of lung endothelial cell migration and proliferation. Mol Cell Biochem 2006; 292: 69-78.
  • 69 Nicklin SA, Baker AH. Efficient vascular endothelial gene transfer following intravenous adenovirus delivery. Mol Ther 2008; 16: 1904-1905.
  • 70 Reynolds PN, Nicklin SA, Kaliberova L. et al. Combined transductional and transcriptional targeting improves the specificity of transgene expression in vivo. Nat Biotechnol 2001; 19: 838-842.
  • 71 Schnittler HJ, Feldmann H. Marburg and Ebola hemorrhagic fevers: does the primary course of infection depend on the accessibility of organ-specific macrophages?. Clin Infect Dis 1998; 27: 404-406.
  • 72 Yee D, McGuire SE, Brunner N. et al. Adenovirusmediated gene transfer of herpes simplex virus thymidine kinase in an ascites model of human breast cancer. Hum Gene Ther 1996; 07: 1251-1257.
  • 73 Tal R, Shaish A, Rofe K. et al. Endothelial-targeted gene transfer of hypoxia-inducible factor-1alpha augments ischemic neovascularization following systemic administration. Mol Ther 2008; 16: 1927-1936.
  • 74 Gall J, Kass-Eisler A, Leinwand L. et al. Adenovirus type 5 and 7 capsid chimera: fiber replacement alters receptor tropism without affecting primary immune neutralization epitopes. J Virol 1996; 70: 2116-2123.
  • 75 Shayakhmetov DM, Lieber A. Dependence of adenovirus infectivity on length of the fiber shaft domain. J Virol 2000; 74: 10274-10286.
  • 76 Shayakhmetov DM, Papayannopoulou T, Stamatoyannopoulos G. et al. Efficient gene transfer into human CD34(+) cells by a retargeted adenovirus vector. J Virol 2000; 74: 2567-2583.
  • 77 Stevenson SC, Rollence M, Marshall-Neff J. et al. Selective targeting of human cells by a chimeric adenovirus vector containing a modified fiber protein. J Virol 1997; 71: 4782-4790.
  • 78 Henry LJ, Xia D, Wilke ME. et al. Characterization of the knob domain of the adenovirus type 5 fiber protein expressed in Escherichia coli. J Virol 1994; 68: 5239-5246.
  • 79 Xia D, Henry LJ, Gerard RD. et al. Crystal structure of the receptor-binding domain of adenovirus type 5 fiber protein at 1.7 A resolution. Structure 1994; 02: 1259-1270.
  • 80 Von Seggern DJ, Kehler J, Endo RI. et al. Complementation of a fibre mutant adenovirus by packaging cell lines stably expressing the adenovirus type 5 fibre protein. J Gen Virol 1998; 79: 1461-1468.
  • 81 Denby L, Work LM, Graham D. et al. Adenoviral serotype 5 vectors pseudotyped with fibers from subgroup D show modified tropism in vitro and in vivo. Hum Gene Ther 2004; 15: 1054-1064.
  • 82 Hay CM, De Leon H, Jafari JD. et al. Enhanced gene transfer to rabbit jugular veins by an adenovirus containing a cyclic RGD motif in the HI loop of the fiber knob. J Vasc Res 2001; 38: 315-323.
  • 83 Jakubczak JL, Rollence ML, Stewart DA. et al. Adenovirus type 5 viral particles pseudotyped with mutagenized fiber proteins show diminished infectivity of coxsackie B-adenovirus receptor-bearing cells. J Virol 2001; 75: 2972-2981.
  • 84 Nicklin SA, Von Seggern DJ, Work LM. et al. Ablating adenovirus type 5 fiber-CAR binding and HI loop insertion of the SIGYPLP peptide generate an endothelial cell-selective adenovirus. Mol Ther 2001; 04: 534-542.
  • 85 Nicklin SA, White SJ, Nicol CG. et al. In vitro and in vivo characterisation of endothelial cell selective adenoviral vectors. J Gene Med 2004; 06: 300-308.
  • 86 Nicklin SA, White SJ, Watkins SJ. et al. Selective targeting of gene transfer to vascular endothelial cells by use of peptides isolated by phage display. Circulation 2000; 102: 231-237.
  • 87 Mahanivong C, Kruger JA, Bian D. et al. A simplified cloning strategy for the generation of an endothelial cell selective recombinant adenovirus vector. J Virol Methods 2006; 135: 127-135.
  • 88 Baker AH, Kritz A, Work LM. et al. Cell-selective viral gene delivery vectors for the vasculature. Exp Physiol 2005; 90: 27-31.
  • 89 Work LM, Nicklin SA, Brain NJ. et al. Development of efficient viral vectors selective for vascular smooth muscle cells. Mol Ther 2004; 09: 198-208.
  • 90 Arcasoy SM, Latoche JD, Gondor M. et al. Polycations increase the efficiency of adenovirus-mediated gene transfer to epithelial and endothelial cells in vitro. Gene Ther 1997; 04: 32-38.
  • 91 Jornot L, Morris MA, Petersen H. et al. N-acetylcysteine augments adenovirus-mediated gene expression in human endothelial cells by enhancing transgene transcription and virus entry. J Gene Med 2002; 04: 54-65.
  • 92 Zhou H, Zeng G, Zhou A. et al. Adenovirus mediated gene transfer of vascular smooth muscle cells and endothelial cells in vitro. Chin Med J (Engl) 1995; 108: 493-496.
  • 93 Zhou H, Zeng G, Zhu X. et al. Enhanced adeno-associated virus vector expression by adenovirus proteincationic liposome complex. A novel and high efficient way to introduce foreign DNA into endothelial cells. Chin Med J (Engl) 1995; 108: 332-337.
  • 94 Hofherr SE, Mok H, Gushiken FC. et al. Polyethylene glycol modification of adenovirus reduces platelet activation, endothelial cell activation, and thrombocytopenia. Hum Gene Ther 2007; 18: 837-848.
  • 95 Ogawara K, Rots MG, Kok RJ. et al. A novel strategy to modify adenovirus tropism and enhance transgene delivery to activated vascular endothelial cells in vitro and in vivo. Hum Gene Ther 2004; 15: 433-443.
  • 96 Seebach J, Madler HJ, Wojciak-Stothard B. et al. Tyrosine phosphorylation and the small GTPase rac cross-talk in regulation of endothelial barrier function. Thromb Haemost 2005; 94: 620-629.
  • 97 Seebach J, Donnert G, Kronstein R. et al. Regulation of endothelial barrier function during flow-induced conversion to an arterial phenotype. Cardiovasc Res 2007; 75: 598-607.