Genetic manipulation in pigs

Current Opinion in Organ Transplantation

Volumn 14, Issue 2, 2009, Pages 148-153

  Sachs, David H ^a   Galli, Cesare ^b  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Genetic engineering; Knockout; Transplantation; Xenograft; Xenotransplantation

Indexed keywords

ALPHA 1,3 GALACTOSYLTRANSFERASE; LENTIVIRUS VECTOR; SMALL INTERFERING RNA; ALPHA 1,3 GALACTOSYLTRANSFERASE 1, PORCINE; ALPHA GALACTOSYL EPITOPE; ALPHA-1,3-GALACTOSYLTRANSFERASE 1, PORCINE; ALPHA-GALACTOSYL EPITOPE; GALACTOSYLTRANSFERASE; TRISACCHARIDE;

BABOON; CELL NUCLEUS TRANSPLANTATION; ENZYME ENGINEERING; EXPERIMENTAL PIG; GENE EXPRESSION; GENE TRANSFER; GENETIC ENGINEERING; GENETIC MANIPULATION; GRAFT SURVIVAL; IMMUNOSUPPRESSIVE TREATMENT; KIDNEY TRANSPLANTATION; KNOCKOUT GENE; MICROINJECTION; NONHUMAN; PRONUCLEAR MICROINJECTION; REVIEW; SOMATIC CELL; SPERM; TRANSGENE; TRANSGENIC ANIMAL; XENOTRANSPLANTATION; ANIMAL; GENE INACTIVATION; GENETIC PROCEDURES; GENETICS; GRAFT REJECTION; HUMAN; IMMUNOLOGY; ORGAN TRANSPLANTATION; SPECIES DIFFERENCE; SWINE; TRANSPLANTATION TOLERANCE; XENOGRAFT;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; GALACTOSYLTRANSFERASES; GENE KNOCKOUT TECHNIQUES; GENETIC TECHNIQUES; GRAFT REJECTION; GRAFT SURVIVAL; HUMANS; ORGAN TRANSPLANTATION; SPECIES SPECIFICITY; SWINE; TRANSPLANTATION TOLERANCE; TRANSPLANTATION, HETEROLOGOUS; TRISACCHARIDES;

EID: 67651043695     PISSN: 10872418     EISSN: 15317013     Source Type: Journal    
DOI: 10.1097/MOT.0b013e3283292549     Document Type: Review

References (58)

1. Cozzi E, Tucker AW, Langford GA, et al. Characterization of pigs transgenic for human decay-accelerating factor. Transplantation 1997; 64:1383-1392. (Pubitemid 27513614)
2. Diamond LE, McCurry KR, Martin MJ, et al. Characterization of transgenic pigs expressing functionally active human CD59 on cardiac endothelium. Transplantation 1996; 61:1241-1249.
3. Lai L, Kolber-Simonds D, Park KW, et al. Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 2002; 295:1089-1092. (Pubitemid 34132242)
4. Phelps CJ, Koike C, Vaught TD, et al. Production of alpha 1,3-galactosyltransferase- deficient pigs. Science 2003; 299:411-414.
5. Kolber-Simonds D, Lai L, Watt SR, et al. Production of alpha-1,3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations. Proc Natl Acad Sci U S A 2004; 101:7335-7340. (Pubitemid 38638033)
6. Hammer RE, Pursel VG, Rexroad CE Jr, et al. Production of transgenic rabbits, sheep and pigs by microinjection. Nature 1985; 315:680-683.
7. Galli C, Lazzari G. The manipulation of gametes and embryos in farm animals. Reprod Domest Anim 2008; 43 (Suppl 2):1-7. The authors provide a review of techniques for assisted reproduction in large animals.
8. McCreath KJ, Howcroft J, Campbell KH, et al. Production of gene-targeted sheep by nuclear transfer from cultured somatic cells. Nature 2000; 405: 1066-1069. (Pubitemid 30447792)
9. Denning C, Burl S, Ainslie A, et al. Deletion of the alpha(1,3)galactosyl transferase (GGTA1) gene and the prion protein (PrP) gene in sheep. Nat Biotechnol 2001; 19:559-562.
10. Klose R, Kemter E, Bedke T, et al. Expression of biologically active human TRAIL in transgenic pigs. Transplantation 2005; 80:222-230. (Pubitemid 41061679)
11. Martin C, Plat M, Nerriere-Daguin V, et al. Transgenic expression of CTLA4-Ig by fetal pig neurons for xenotransplantation. Transgenic Res 2005; 14:373-384. (Pubitemid 41125388)
12. Kues WA, Schwinzer R, Wirth D, et al. Epigenetic silencing and tissue independent expression of a novel tetracycline inducible system in doubletransgenic pigs. FASEB J 2006; 20:1200-1202. This study provides preliminary evidence of the possibility to use inducible promoters in pigs. (Pubitemid 44943871)
13. Webster NL, Forni M, Bacci ML, et al. Multitransgenic pigs expressing three fluorescent proteins produced with high efficiency by sperm mediated gene transfer. Mol Reprod Dev 2005; 72:68-76. (Pubitemid 41026308)
14. Wu Z, Li Z, Yang J. Transient transgene transmission to piglets by intrauterine insemination of spermatozoa incubated with DNA fragments. Mol Reprod Dev 2008; 75:26-32. This study questions the long-term expression of transgenes inserted by SMGT. (Pubitemid 350223987)
15. Manzini S, Vargiolu A, Stehle IM, et al. Genetically modified pigs produced with a nonviral episomal vector. Proc Natl Acad Sci USA 2006; 103:17672-17677. (Pubitemid 44867989)
16. Kurome M, Ueda H, Tomii R, et al. Production of transgenic-clone pigs by the combination of ICSI-mediated gene transfer with somatic cell nuclear transfer. Transgenic Res 2006; 15:229-240.
17. Moreira PN, Giraldo P, Cozar P, et al. Efficient generation of transgenic mice with intact yeast artificial chromosomes by intracytoplasmic sperm injection. Biol Reprod 2004; 71:1943-1947. (Pubitemid 39586940)
18. Whitelaw CB, Radcliffe PA, Ritchie WA, et al. Efficient generation of transgenic pigs using equine infectious anaemia virus (EIAV) derived vector. FEBS Lett 2004; 571:233-236.
19. Hofmann A, Kessler B, Ewerling S, et al. Epigenetic regulation of lentiviral transgene vectors in a large animal model. Mol Ther 2006; 13:59-66. (Pubitemid 41763483)
20. Rogers CS, Hao Y, Rokhlina T, et al. Production of CFTR-null and CFTRdeltaF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer. J Clin Invest 2008; 118:1571-1577. This study provides evidence of a high gene-targeting efficiency using AAV in cells with very low expression of the target gene. The CFTR allele was inactivated or replaced by a mutated form.
21. Lagutina I, Lazzari G, Duchi R, et al. Comparative aspects of somatic cell nuclear transfer with conventional and zona-free method in cattle, horse, pig and sheep. Theriogenology 2007; 67:90-98. (Pubitemid 44854141)
22. Brunetti D, Perota A, Lagutina I, et al. Transgene expression of green fluorescent protein and germ line transmission in cloned pigs derived from in vitro transfected adult fibroblasts. Cloning Stem Cells 2008; 10:409-420. This study combines somatic cell genetic modification and zona-free SCNT for the production of pigs expressing high levels of GFP that is maintained in their offspring.
23. Lagutina I, Lazzari G, Galli C. Birth of cloned pigs from zona-free nuclear transfer blastocysts developed in vitro before transfer. Cloning Stem Cells 2006; 8:283-293. (Pubitemid 46146036)
24. Vajta G, Kragh PM, Mtango NR, Callesen H. Hand-made cloning approach: potentials and limitations. Reprod Fertil Dev 2005; 17:97-112. (Pubitemid 40103668)
25. Kragh PM, Du Y, Corydon TJ, et al. Efficient in vitro production of porcine blastocysts by handmade cloning with a combined electrical and chemical activation. Theriogenology 2005; 64:1536-1545. (Pubitemid 41338622)
26. Kurome M, Ishikawa T, Tomii R, et al. Production of transgenic and nontransgenic clones in miniature pigs by somatic cell nuclear transfer. J Reprod Dev 2008; 54:156-163. This study compares cloning using minipigs or commercial breeds as recipients and found the latter to be more efficient. Moreover, when transgenic cells are used, the efficiency dropped. (Pubitemid 351918066)
27. Estrada JL, Collins B, York A, et al. Successful cloning of the Yucatan minipig using commercial/occidental breeds as oocyte donors and embryo recipients. Cloning Stem Cells 2008; 10:287-296. This study provides evidence of the low efficiency of cloning by nuclear transfer from Yucatan minipigs using commercial breeds as recipients. (Pubitemid 351748828)
28. Nottle MB, Beebe LF, Harrison SJ, et al. Production of homozygous alpha-1,3- galactosyltransferase knockout pigs by breeding and somatic cell nuclear transfer. Xenotransplantation 2007; 14:339-344. This study generated GAL-KO pigs by a breeding strategy of heterozygous founders to minimize the level of inbreeding.
29. Clark KJ, Carlson DF, Foster LK, et al. Enzymatic engineering of the porcine genome with transposons and recombinases. BMC Biotechnol 2007; 7:42.
30. Santoni de Sio FR, Cascio P, Zingale A, et al. Proteasome activity restricts lentiviral gene transfer into hematopoietic stem cells and is down-regulated by cytokines that enhance transduction. Blood 2006; 107:4257-4265. (Pubitemid 43801349)
31. Santoni de Sio FR, Gritti A, Cascio P, et al. Lentiviral vector gene transfer is limited by the proteasome at postentry steps in various types of stem cells. Stem Cells 2008; 26:2142-2152. This study demonstrated the efficacy of proteasome inhibitors in increasing the lentiviral integration.
32. Lombardo A, Genovese P, Beausejour CM, et al. Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nat Biotechnol 2007; 25:1298-1306. This study described the use of zinc finger nucleases to significantly increase the efficiency of homologous recombination. (Pubitemid 350076515)
33. Porteus MH. Mammalian gene targeting with designed zinc finger nucleases. Mol Ther 2006; 13:438-446.
34. Fang J, Qian JJ, Yi S, et al. Stable antibody expression at therapeutic levels using the 2A peptide. Nat Biotechnol 2005; 23:584-590. (Pubitemid 41724897)
35. d'Apice AJ, Cowan PJ. Gene-modified pigs. Xenotransplantation 2008; 15:87-90. This is an opinion paper on the future directions of xenotransplantation research.
36. Dieckhoff B, Petersen B, Kues WA, et al. Knockdown of porcine endogenous retrovirus (PERV) expression by PERV-specific shRNA in transgenic pigs. Xenotransplantation 2008; 15:36-45. This study demonstrated the possibility to use siRNA to knock down PERV transcripts, thus reducing the probability of PERV transmission during xenotransplantation. (Pubitemid 351360240)
37. Jonsson SR, LaRue RS, Stenglein MD, et al. The restriction of zoonotic PERV transmission by human APOBEC3G. PLoS ONE 2007; 2:e893.
38. Diamond LE, Quinn CM,Martin MJ, et al. A human CD46 transgenic pig model system for the study of discordant xenotransplantation. Transplantation 2001; 71:132-142.
39. Byrne GW, McCurry KR, Martin MJ, et al. Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement- mediated damage. Transplantation 1997; 63:149-155.
40. Sachs DH, Fishman JA. Xenotransplantation. In: Brenner BM, editor. Brenner & Rector's The Kidney. Philadelphia: Saunders Elsevier; 2008. pp. 2183- 2198. This chapter provides a recent and comprehensive review of the field of xenotransplantation with emphasis on an alternative source of renal transplants.
41. Lam TT, Hausen B, Hook L, et al. The effect of soluble complement receptor type 1 on acute humoral xenograft rejection in hDAF-transgenic pig-to-primate life-supporting kidney xenografts. Xenotransplantation 2005; 12:20-29. (Pubitemid 40105145)
42. McGregor CG, Davies WR, Oi K, et al. Cardiac xenotransplantation: recent preclinical progress with 3-month median survival. J Thorac Cardiovasc Surg 2005; 130:844-851. (Pubitemid 41265729)
43. Shimizu A, Yamada K, Yamamoto S, et al. Thrombotic microangiopathic glomerulopathy in human decay accelerating factor-transgenic swine-to-baboon kidney xenografts. J Am Soc Nephrol 2005; 16:2732-2745.
44. Byrne GW, Davies WR, Oi K, et al. Increased immunosuppression, not anticoagulation, extends cardiac xenograft survival. Transplantation 2006; 82:1787-1791. The results of this study suggest that the current limitations of organ xenotransplant survival are more likely to involve better control of the immune system rather than of the coagulation system. (Pubitemid 46035668)
45. Chen G, Sun H, Yang H, et al. The role of antinon-Gal antibodies in the development of acute humoral xenograft rejection of hDAF transgenic porcine kidneys in baboons receiving anti-Gal antibody neutralization therapy. Transplantation 2006; 81:273-283.
46. Forte P, Baumann BC, Weiss EH, Seebach JD. HLA-E expression on porcine cells: protection from human NK cytotoxicity depends on peptide loading. Am J Transplant 2005; 5:2085-2093. (Pubitemid 41648455)
47. Lilienfeld BG, Crew MD, Forte P, et al. Transgenic expression of HLA-E single chain trimer protects porcine endothelial cells against human natural killer cellmediated cytotoxicity. Xenotransplantation 2007; 14:126-134. This study provides in-vitro evidence that expression of HLA-E on pig endothelial cells inhibits their destruction by human NK cells. (Pubitemid 46457451)
48. Diaz-Roman TM, Manez R, Lopez-Pelaez E, et al. Human DAF on pig cells protects against human and nonhuman primate sera cytotoxicity mediated by exogenous or endogenous complement, as determined by flow cytometry. Transpl Immunol 2006; 16:125-130. (Pubitemid 44088621)
49. Manzi L, Montano R, Abad MJ, et al. Expression of human soluble complement receptor 1 by a pig endothelial cell line inhibits lysis by human serum. Xenotransplantation 2006; 13:75-79.
50. Hering BJ, Wijkstrom M, Graham ML, et al. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat Med 2006; 12:301-303. This study has achieved survival and function of adult porcine islets from genetically unmodified pigs in cynomolgus monkeys of over 100 days. (Pubitemid 43355076)
51. Komoda H, Miyagawa S, Omori T, et al. Survival of adult islet grafts from transgenic pigs with N-acetylglucosaminyltransferase-III (GnT-III) in cynomolgus monkeys. Xenotransplantation 2005; 12:209-216. (Pubitemid 40524981)
52. Chen G, Qian H, Starzl T, et al. Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys. Nat Med 2005; 11:1295-1298. (Pubitemid 41752909)
53. Kuwaki K, Tseng YL, Dor FJ, et al. Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience. Nat Med 2005; 11:29-31. This study presents the first results obtained using GalT-KO animals as a source of heterotopic cardiac xenografts to baboons. Survival of nonlife-supporting hearts of up to 179 days is reported using chronic immunosuppression. (Pubitemid 40215833)
54. Kuwaki K, Knosalla C, Dor FJ, et al. Suppression of natural and elicited antibodies in pig-to-baboon heart transplantation using a human antihuman CD154 mAb-based regimen. Am J Transplant 2004; 4:363-372. (Pubitemid 38282291)
55. Tseng YL, Kuwaki K, Dor FJ, et al. alpha1,3-Galactosyltransferase geneknockout pig heart transplantation in baboons with survival approaching 6 months. Transplantation 2005; 80:1493-1500. (Pubitemid 41803633)
56. Shimizu A, Hisashi Y, Kuwaki K, et al. Thrombotic microangiopathy associated with humoral rejection of cardiac xenografts from alpha1,3-galactosyltransferase gene-knockout pigs in baboons. Am J Pathol 2008; 172:1471-1481. The results of this study indicate that the characteristic thrombotic microangiopathy seen histologically in porcine heart xenografts transplanted into baboons are associated with antibody-mediated rejection, which may be the primary cause of the lesions. (Pubitemid 351793341)
57. Yamada K, Yazawa K, Shimizu A, et al. 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 2005; 11:32-34. This study presents the first results obtained using GalT-KO animals as a source of orthotopic renal xenografts to baboons. Survival of life-supporting kidneys of up to 83 days is reported using a treatment regimen directed toward the induction of tolerance through cotransplantation of vascularized thymic tissue. (Pubitemid 40215834)
58. Mezrich JD, Haller GW, Arn JS, et al. Histocompatible miniature swine: an inbred large-animal model. Transplantation 2003; 75:904-907.