The production of multi-transgenic pigs: update and perspectives for xenotransplantation

Transgenic Research

Volumn 25, Issue 3, 2016, Pages 361-374

  Niemann, Heiner ^a,b   Petersen, Bjoern ^a,b  

^a FEDERAL RESEARCH INSTITUTE FOR ANIMAL HEALTH   (Germany)

^b HANNOVER MEDICAL SCHOOL   (Germany)

Author keywords

Anti coagulant strategy; DNA nucleases; Hemeoxygenase 1 gene; Human organ shortage; Long term survival of porcine xenografts; Somatic cell nuclear transfer

Indexed keywords

ANIMAL; GENETIC ENGINEERING; GENETICS; GROWTH, DEVELOPMENT AND AGING; HUMAN; ORGAN TRANSPLANTATION; PIG; TRANSGENIC ANIMAL; TRENDS; XENOGRAFT;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; GENETIC ENGINEERING; HUMANS; ORGAN TRANSPLANTATION; SWINE; TRANSPLANTATION, HETEROLOGOUS;

EID: 84955575666     PISSN: 09628819     EISSN: 15739368     Source Type: Journal    
DOI: 10.1007/s11248-016-9934-8     Document Type: Review

References (89)

1. Ahrens HE, Petersen B, Herrmann D, Lucas-Hahn A, Hassel P, Ziegler M et al (2015a) siRNA mediated knockdown of tissue factor expression in pigs for xenotransplantation. Am J Transplant 15:1407–1414
2. Ahrens HE, Petersen B, Ramackers W, Petkov S, Herrmann D, Hauschild-Quintern J et al (2015b) Kidneys from α1,3-galactosyltransferase knockout/human heme oxygenase-1/human A20 transgenic pigs are protected from rejection during ex vivo perfusion with human blood. Transplant Direct 1:1–8
3. Bach FH, Ferran C, Hechenleitner P, Mark W, Koyamada N, Miyatake T et al (1997) Accommodation of vascularized xenografts: expression of “protective genes” by donor endothelial cells in a host Th2 cytokine environment. Nat Med 3:196–204
4. Balla G, Jacob HS, Balla J, Rosenberg M, Nath K, Apple F et al (1992) Ferritin: a cytoprotective antioxidant strategem of endothelium. J Biol Chem 267:18148–18153
5. Banz Y, Cung T, Korchagina EY, Bovin NV, Haeberli A, Rieben R (2005) Endothelial cell protection and complement inhibition in xenotransplantation: a novel in vitro model using whole blood. Xenotransplantation 12:434–443
6. Brune B, Ullrich V (1987) Inhibition of platelet aggregation by carbon monoxide is mediated by activation of guanylate cyclase. Mol Pharmacol 32:497–504
7. Byrne GW, Stalboerger PG, Davila E, Heppelmann CJ, Gazi MH, McGregor HC et al (2008) Proteomic identification of non-Gal antibody targets after pig-to-primate cardiac xenotransplantation. Xenotransplantation 15:268–276
8. Byrne GW, Stalboerger PG, Du Z, Davis TR, McGregor CG (2011) Identification of new carbohydrate and membrane protein antigens in cardiac xenotransplantation. Transplantation 91:287–292
9. Byrne GW, Du Z, Stalboerger P, Kogelberg H, McGregor CG (2014) Cloning and expression of porcine beta1,4 N-acetylgalactosaminyl transferase encoding a new xenoreactive antigen. Xenotransplantation 21:543–554
10. Carlson DF, Tan W, Lillico SG, Stverakova D, Proudfoot C, Christian M et al (2012) Efficient TALEN-mediated gene knockout in livestock. Proc Natl Acad Sci USA 109:17382–17387
11. Chou H, Takematsu H, Diaz S, Iber J, Nickerson E, Wright KL et al (1998) A mutation in human CMP-sialic acid hydroxylase occurred after the Homo-Pan divergence. Proc Natl Acad Sci USA 95:11751–11756
12. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N et al (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339:819–823
13. Cooper DK, Satyananda V, Ekser B, van der Windt DJ, Hara H, Ezzelarab MB et al (2014) Progress in pig-to-non-human primate transplantation models (1998–2013): a comprehensive review of the literature. Xenotransplantation 21:397–419
14. Crikis S, Cowan PJ, d’Apice AJ (2006) Intravascular thrombosis in discordant xenotransplantation. Transplantation 82:1119–1123
15. Dai Y, Vaught TD, Boone J, Chen SH, Phelps CJ, Ball S et al (2002) Targeted disruption of the alpha1,3-galactosyltransferase gene in cloned pigs. Nat Biotechnol 20:251–255
16. d’Apice AJ, Cowan PJ (2008) Xenotransplantation: the next generation of engineered animals. Transpl Immunol 21:111–115
17. Davila E, Byrne GW, LaBreche PT, McGregor HC, Schwab AK, Davies WR et al (2006) T-cell responses during pig-to-primate xenotransplantation. Xenotransplantation 13:31–40
18. Esquivel EL, Maeda A, Eguchi H, Asada M, Sugiyama M, Manabe C et al (2015) Suppression of human macrophage-mediated cytotoxicity by transgenic swine endothelial cell expression of HLA-G. Transpl Immunol 32:109–115
19. Estrada JL, Martens G, Li P, Adams A, Newell KA, Ford ML et al (2015) Evaluation of human and non-human primate antibody binding to pig cells lacking GGTA1/CMAH/beta4GalNT2 genes. Xenotransplantation 22:194–202
20. Fu Y, Sander JD, Reyon D, Cascio VM, Joung JK (2014) Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol 32:279–284
21. Fujimura T, Kurome M, Murakami H, Takahagi Y, Matsunami K, Shimanuki S et al (2004) Cloning of the transgenic pigs expressing human decay accelerating factor and N-acetylglucosaminyltransferase III. Cloning Stem Cells 6:294–301
22. Galili U (1993) Interaction of the natural anti-Gal antibody with alpha-galactosyl epitopes: a major obstacle for xenotransplantation in humans. Immunol Today 14:480–482
23. Garrels W, Mates L, Holler S, Dalda A, Taylor U, Petersen B et al (2011) Germline transgenic pigs by Sleeping Beauty transposition in porcine zygotes and targeted integration in the pig genome. PLoS ONE 6:e23573
24. Goto M, Groth CG, Nilsson B, Korsgren O (2004) Intraportal pig islet xenotransplantation into athymic mice as an in vivo model for the study of the instant blood-mediated inflammatory reaction. Xenotransplantation 11:195–202
25. Guilinger JP, Thompson DB, Liu DR (2014) Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat Biotechnol 32:577–582
26. Hai T, Teng F, Guo R, Li W, Zhou Q (2014) One-step generation of knockout pigs by zygote injection of CRISPR/Cas system. Cell Res 24:372–375
27. Harris DG, Quinn KJ, French BM, Schwartz E, Kang E, Dahi S et al (2015) Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood. Xenotransplantation 22:102–111
28. Hauschild J, Petersen B, Santiago Y, Queisser AL, Carnwath JW, Lucas-Hahn A et al (2011) Efficient generation of a biallelic knockout in pigs using zinc-finger nucleases. Proc Natl Acad Sci USA 108:12013–12017
29. Hauschild-Quintern J, Petersen B, Queisser AL, Lucas-Hahn A, Schwinzer R, Niemann H (2013a) Gender non-specific efficacy of ZFN mediated gene targeting in pigs. Transgenic Res 22:1–3
30. Hauschild-Quintern J, Petersen B, Cost GJ, Niemann H (2013b) Gene knockout and knockin by zinc-finger nucleases: current status and perspectives. Cell Mol Life Sci 70:2969–2983
31. Horvath-Arcidiacono JA, Porter CM, Bloom ET (2006) Human NK cells can lyse porcine endothelial cells independent of their expression of Galalpha(1,3)-Gal and killing is enhanced by activation of either effector or target cells. Xenotransplantation 13:318–327
32. Ide K, Ohdan H, Kobayashi T, Hara H, Ishiyama K, Asahara T (2005) Antibody- and complement-independent phagocytotic and cytolytic activities of human macrophages toward porcine cells. Xenotransplantation 12:181–188
33. Inverardi L, Clissi B, Stolzer AL, Bender JR, Sandrin MS, Pardi R (1997) Human natural killer lymphocytes directly recognize evolutionarily conserved oligosaccharide ligands expressed by xenogeneic tissues. Transplantation 63:1318–1330
34. Iwase H, Ezzelarab MB, Ekser B, Cooper DK (2014) The role of platelets in coagulation dysfunction in xenotransplantation, and therapeutic options. Xenotransplantation 21:201–220
35. Izsvak Z, Chuah MK, Vandendriessche T, Ivics Z (2009) Efficient stable gene transfer into human cells by the Sleeping Beauty transposon vectors. Methods 49:287–297
36. Jaattela M, Mouritzen H, Elling F, Bastholm L (1996) A20 zinc finger protein inhibits TNF and IL-1 signaling. J Immunol 156:1166–1173
37. Kim D, Bae S, Park J, Kim E, Kim S, Yu HR et al (2015) Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells. Nat Methods 12:237–243
38. Klymiuk N, van Buerck L, Bahr A, Offers M, Kessler B, Wuensch A et al (2012) Xenografted islet cell clusters from INSLEA29Y transgenic pigs rescue diabetes and prevent immune rejection in humanized mice. Diabetes 61:1527–1532
39. Kuwaki K, Tseng YL, Dor FJ, Shimizu A, Houser SL, Sanderson TM et al (2005) Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience. Nat Med 11:29–31
40. Lai L, Kolber-Simonds D, Park KW, Cheong HT, Greenstein JL, Im GS et al (2002) Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 295:1089–1092
41. LaMattina JC, Burdorf L, Zhang T, Rybak E, Cheng X, Munivenkatappa R et al (2014) Pig-to-baboon liver xenoperfusion utilizing GalTKO.hCD46 pigs and glycoprotein Ib blockade. Xenotransplantation 21:274–286
42. Larsen CP, Pearson TC, Adams AB, Tso P, Shirasugi N, Strobert E et al (2005) Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am J Transplant 5:443–453
43. Lee KF, Salvaris EJ, Roussel JC, Robson SC, d’Apice AJ, Cowan PJ (2008) Recombinant pig TFPI efficiently regulates human tissue factor pathways. Xenotransplantation 15:191–197
44. Lee KG, Lee H, Ha JM, Lee YK, Kang HJ, Park CG et al (2012) Increased human tumor necrosis factor-alpha levels induce procoagulant change in porcine endothelial cells in vitro. Xenotransplantation 19:186–195
45. Li P, Estrada JL, Burlak C, Montgomery J, Butler JR, Santos RM et al (2015) Efficient generation of genetically distinct pigs in a single pregnancy using multiplexed single-guide RNA and carbohydrate selection. Xenotransplantation 22:20–31
46. Lillico SG, Proudfoot C, Carlson DF, Stverakova D, Neil C, Blain C et al (2013) Live pigs produced from genome edited zygotes. Sci Rep 3:2847
47. Lin CC, Chen D, McVey JH, Cooper DK, Dorling A (2008) Expression of tissue factor and initiation of clotting by human platelets and monocytes after incubation with porcine endothelial cells. Transplantation 86:702–709
48. Loveland BE, Milland J, Kyriakou P, Thorley BR, Christiansen D, Lanteri MB et al (2004) Characterization of a CD46 transgenic pig and protection of transgenic kidneys against hyperacute rejection in non-immunosuppressed baboons. Xenotransplantation 11:171–183
49. Luther T, Flossel C, Mackman N, Bierhaus A, Kasper M, Albrecht S et al (1996) Tissue factor expression during human and mouse development. Am J Pathol 149:101–113
50. Lutz J, le Luong A, Strobl M, Deng M, Huang H, Anton M et al (2008) The A20 gene protects kidneys from ischaemia/reperfusion injury by suppressing pro-inflammatory activation. J Mol Med (Berl) 86:1329–1339
51. Ma X, Ye B, Gao F, Liang Q, Dong Q, Liu Y et al (2012) Tissue factor knockdown in porcine islets: an effective approach to suppressing the instant blood-mediated inflammatory reaction. Cell Transplant 21:61–71
52. Miller JC, Tan S, Qiao G, Barlow KA, Wang J, Xia DF et al (2011) A TALE nuclease architecture for efficient genome editing. Nat Biotechnol 29:143–148
53. Miwa Y, Kobayashi T, Nagasaka T, Liu D, Yu M, Yokoyama I et al (2004) Are N-glycolylneuraminic acid (Hanganutziu–Deicher) antigens important in pig-to-human xenotransplantation? Xenotransplantation 11:247–253
54. Mueller BM, Reisfeld RA, Edgington TS, Ruf W (1992) Expression of tissue factor by melanoma cells promotes efficient hematogenous metastasis. Proc Natl Acad Sci USA 89:11832–11836
55. Niemann H, Verhoeyen E, Wonigeit K, Lorenz R, Hecker J, Schwinzer R et al (2001) Cytomegalovirus early promoter induced expression of hCD59 in porcine organs provides protection against hyperacute rejection. Transplantation 72:1898–1906
56. Oropeza M, Petersen B, Carnwath JW, Lucas-Hahn A, Lemme E, Hassel P et al (2009) Transgenic expression of the human A20 gene in cloned pigs provides protection against apoptotic and inflammatory stimuli. Xenotransplantation 16:522–534
57. Osterud B, Rapaport SI (1977) Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation. Proc Natl Acad Sci USA 74:5260–5264
58. Padler-Karavani V, Yu H, Cao H, Chokhawala H, Karp F, Varki N et al (2008) Diversity in specificity, abundance, and composition of anti-Neu5Gc antibodies in normal humans: potential implications for disease. Glycobiology 18:818–830
59. Parry GC, Erlich JH, Carmeliet P, Luther T, Mackman N (1998) Low levels of tissue factor are compatible with development and hemostasis in mice. J Clin Invest 101:560–569
60. Petersen B, Niemann H (2015) Molecular scissors and their application in genetically modified farm animals. Transgenic Res 24:381–396
61. Petersen B, Carnwath JW, Niemann H (2009a) The perspectives for porcine-to-human xenografts. Comp Immunol Microbiol Infect Dis 32:91–105
62. Petersen B, Ramackers W, Tiede A, Lucas-Hahn A, Herrmann D, Barg-Kues B et al (2009b) Pigs transgenic for human thrombomodulin have elevated production of activated protein C. Xenotransplantation 16:486–495
63. Petersen B, Ramackers W, Lucas-Hahn A, Lemme E, Hassel P, Queisser AL et al (2011) Transgenic expression of human heme oxygenase-1 in pigs confers resistance against xenograft rejection during ex vivo perfusion of porcine kidneys. Xenotransplantation 18:355–368
64. Phelps CJ, Koike C, Vaught TD, Boone J, Wells KD, Chen SH et al (2003) Production of alpha 1,3-galactosyltransferase-deficient pigs. Science 299:411–414
65. Reyes LM, Estrada JL, Wang ZY, Blosser RJ, Smith RF, Sidner RA et al (2014) Creating class I MHC-null pigs using guide RNA and the Cas9 endonuclease. J Immunol 193:5751–5757
66. Rieben R, Seebach JD (2005) Xenograft rejection: IgG1, complement and NK cells team up to activate and destroy the endothelium. Trends Immunol 26:2–5
67. Roussel JC, Moran CJ, Salvaris EJ, Nandurkar HH, d’Apice AJ, Cowan PJ (2008) Pig thrombomodulin binds human thrombin but is a poor cofactor for activation of human protein C and TAFI. Am J Transplant 8:1101–1112
68. Ryter SW, Choi AM (2013) Carbon monoxide: present and future indications for a medical gas. Korean J Intern Med 28:123–140
69. Salama A, Evanno G, Harb J, Soulillou JP (2015) Potential deleterious role of anti-Neu5Gc antibodies in xenotransplantation. Xenotransplantation 22:85–94
70. Scobie L, Padler-Karavani V, Le Bas-Bernardet S, Crossan C, Blaha J, Matouskova M et al (2013) Long-term IgG response to porcine Neu5Gc antigens without transmission of PERV in burn patients treated with porcine skin xenografts. J Immunol 191:2907–2915
71. Song HY, Rothe M, Goeddel DV (1996) The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation. Proc Natl Acad Sci USA 93:6721–6725
72. Taylor FB Jr, Chang A, Ruf W, Morrissey JH, Hinshaw L, Catlett R et al (1991) Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 33:127–134
73. Tenhunen R, Ross ME, Marver HS, Schmid R (1970) Reduced nicotinamide-adenine dinucleotide phosphate dependent biliverdin reductase: partial purification and characterization. Biochemistry 9:298–303
74. Mohiuddin MM, Singh AK, Corcoran PC, Hoyt RF, Thomas, ML, III, Ayares D, et al. (2014) Genetically engineered pigs and target-specific immunomodulation provide significant graft survival and hope for clinical cardiac xenotransplantation. J Thorac Cardiovasc Surg 148:1106–1113 (discussion 1113–1114)
75. Toomey JR, Kratzer KE, Lasky NM, Stanton JJ, Broze GJ Jr (1996) Targeted disruption of the murine tissue factor gene results in embryonic lethality. Blood 88:1583–1587
76. Tsai SQ, Wyvekens N, Khayter C, Foden JA, Thapar V, Reyon D et al (2014) Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nat Biotechnol 32:569–576
77. Urnov FD, Miller JC, Lee YL, Beausejour CM, Rock JM, Augustus S et al (2005) Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435:646–651
78. Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD (2010) Genome editing with engineered zinc finger nucleases. Nat Rev Genet 11:636–646
79. Weiss EH, Lilienfeld BG, Muller S, Muller E, Herbach N, Kessler B et al (2009) HLA-E/human beta2-microglobulin transgenic pigs: protection against xenogeneic human anti-pig natural killer cell cytotoxicity. Transplantation 87:35–43
80. Wheeler DG, Joseph ME, Mahamud SD, Aurand WL, Mohler PJ, Pompili VJ et al (2012) Transgenic swine: expression of human CD39 protects against myocardial injury. J Mol Cell Cardiol 52:958–961
81. Whitworth KM, Lee K, Benne JA, Beaton BP, Spate LD, Murphy SL et al (2014) Use of the CRISPR/Cas9 system to produce genetically engineered pigs from in vitro-derived oocytes and embryos. Biol Reprod 91:78
82. Wuensch A, Baehr A, Bongoni AK, Kemter E, Blutke A, Baars W et al (2014) Regulatory sequences of the porcine THBD gene facilitate endothelial-specific expression of bioactive human thrombomodulin in single- and multitransgenic pigs. Transplantation 97:138–147
83. Xin J, Yang H, Fan N, Zhao B, Ouyang Z, Liu Z et al (2013) Highly efficient generation of GGTA1 biallelic knockout inbred mini-pigs with TALENs. PLoS ONE 8:e84250
84. Yamada K, Yazawa K, Shimizu A, Iwanaga T, Hisashi Y, Nuhn M et al (2005) Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue. Nat Med 11:32–34
85. Yang YG, Sykes M (2007) Xenotransplantation: current status and a perspective on the future. Nat Rev Immunol 7:519–531
86. Yet SF, Tian R, Layne MD, Wang ZY, Maemura K, Solovyeva M et al (2001) Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice. Circ Res 89:168–173
87. Zayed H, Izsvak Z, Walisko O, Ivics Z (2004) Development of hyperactive sleeping beauty transposon vectors by mutational analysis. Mol Ther 9:292–304
88. Zetsche B, Gootenberg JS, Abudayyeh OO, Slaymaker IM, Makarova KS, Essletzbichler P et al (2015) Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell 163(3):759–771
89. Zhou J, Shen B, Zhang W, Wang J, Yang J, Chen L et al (2014) One-step generation of different immunodeficient mice with multiple gene modifications by CRISPR/Cas9 mediated genome engineering. Int J Biochem Cell Biol 46:49–55