Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Commercial applications of nuclear transfer cloning: three examples

Erik J. Forsberg
+ Author Affiliations
- Author Affiliations

Infigen, Inc., 1825 Infinity Drive, DeForest, WI 53532, USA. Email: eforsberg@infigen.com

Reproduction, Fertility and Development 17(2) 59-68 https://doi.org/10.1071/RD04114
Submitted: 1 August 2004  Accepted: 1 October 2004   Published: 1 January 2005

Abstract

Potential applications of cloning go well beyond the popularly envisioned replication of valuable animals. This is because targeted genetic modifications can be made in donor cells before nuclear transfer. Applications that are currently being pursued include therapeutic protein production in the milk and blood of transgenic cloned animals, the use of cells, tissues and organs from gene-modified animals for transplantation into humans and genetically modified livestock that produce healthier and safer products in an environmentally friendly manner. Commercial and social acceptance of one or more of these early cloning applications will lead to yet unimagined applications of nuclear transfer technology. The present paper summarises progress on three additional applications of nuclear transfer, namely the development of male livestock that produce single-sex sperm, the transfer of immune responses from animals to their clones to permit the production of unlimited supplies of unique polyclonal antibodies, and the generation of genetically modified animals that accurately mimic human diseases for the purpose of developing new therapies. However, the myriad applications of cloning will require appropriate safeguards to ensure safe, humane and responsible outcomes of the technology.


References

Aiello, R. J. , Nevin, D. N. , Ebert, D. L. , Uelmen, P. J. , Kaiser, M. E. , MacCluer, J. W. , Blangero, J. , Dyer, T. D. , and Attie, A. D. (1994). Apolipoprotein B and a second major gene locus contribute to phenotypic variation of spontaneous hypercholesterolemia in pigs. Arterioscler. Thromb. 14, 409–419.
PubMed | Forsberg E. J., Eilertsen K. J., Bishop M. D., Zheng Y., and Leno G. H. (2002a). Sex-specific selection of sperm from transgenic animals. World Intellectual Property Organization patent publication no. WO-02077637A1. (Infigen, Inc.: DeForest, WI, USA.)

Forsberg, E. J. , Strelchenko, N. S. , Augenstein, M. L. , Betthauser, J. M. , and Childs, L. A. , et al. (2002b). Production of cloned cattle from in vitro systems. Biol. Reprod. 67, 327–333.
PubMed | Forsberg E. J., Leno G. H., Betthauser J., Eilertsen K., and Bishop M. D. (2004). Immune response replication in cloned animals. US patent application no. US20040055025A1. (Infigen, Inc.: DeForest, WI, USA.)

Glass, C. K. , and Witztum, J. L. (2001). Atherosclerosis: the road ahead. Cell 104, 503–516.
Crossref | GoogleScholarGoogle Scholar | PubMed | Rapacz J., and Hasler-Rapacz J. (1989). Animal models: the pig. In ‘Genetic Factors in Atherosclerosis: Approaches and Model Systems’. (Eds R. S. Sparkes and A. J. Lusis.) pp. 139–169. (Karger: Basel, Switzerland.)

Rapacz, J. , Hasler-Rapacz, J. , Taylor, K. M. , Checovich, W. J. , and Attie, A. D. (1986). Lipoprotein mutations in pigs are associated with elevated plasma cholesterol and atherosclerosis. Science 234, 1573–1577.
PubMed |

Ratcliff, R. , Evans, M. J. , Cuthbert, A. W. , MacVinish, L. J. , Foster, D. , Anderson, J. R. , and Colledge, W. H. (1993). Production of a severe cystic fibrosis mutation in mice by gene targeting. Nat. Genet. 4, 35–41.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Rozmahel, R. , Wilschanski, M. , Matin, A. , Plyte, S. , and Oliver, M. , et al. (1996). Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor. Nat. Genet. 12, 280–287.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Salvetti, M. , Ristori, G. , Bomprezzi, R. , Pozzilli, P. , and Leslie, R. D. (2000). Twins: mirrors of the immune system. Immunol. Today 21, 342–347.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Saxena, V. K. , Singh, H. , Pal, S. K. , and Kumar, S. (1997). Genetic studies on primary antibody response to sheep erythrocytes in guinea fowl. Br. Poult. Sci. 38, 156–158.
PubMed |

Sedivy, J. M. , and Dutriaux, A. (1999). Gene targeting and somatic cell genetics: a rebirth or a coming of age? Trends Genet. 15, 88–90.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Slifka, M. K. , and Ahmed, R. (1996). Long-term humoral immunity against viruses: revisiting the issue of plasma cell longevity. Trends Microbiol. 4, 394–400.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Slifka, M. K. , Matloubian, M. , and Ahmed, R. (1995). Bone marrow is a major site of long-term antibody production after acute viral infection. J. Virol. 69, 1895–1902.
PubMed |

Snouwaert, J. N. , Brigman, K. K. , Latour, A. M. , Malouf, N. N. , Boucher, R. C. , Smithies, O. , and Koller, B. H. (1992). An animal model for cystic fibrosis made by gene targeting. Science 257, 1083–1088.
PubMed |

Southern, P. J. , and Berg, P. (1982). Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J. Mol. Appl. Genet. 1, 327–341.
PubMed |

Tebbutt, S. J. , Wardle, C. J. , Hill, D. F. , and Harris, A. (1995). Molecular analysis of the ovine cystic fibrosis transmembrane conductance regulator gene. Proc. Natl Acad. Sci. USA 92, 2293–2297.
PubMed |

van Doorninck, J. H. , French, P. J. , Verbeek, E. , Peters, R. H. , Morreau, H. , Bijman, J. , and Scholte, B. J. (1995). A mouse model for the cystic fibrosis delta F508 mutation. EMBO J. 14, 4403–4411.
PubMed |

Veniant, M. M. , Withycombe, S. , and Young, S. G. (2001). Lipoprotein size and atherosclerosis susceptibility in Apoe(−/−) and Ldlr(−/−) mice. Arterioscler. Thromb. Vasc. Biol. 21, 1567–1570.
PubMed |

Ventela, S. , Toppari, J. , and Parvinen, M. (2003). Intercellular organelle traffic through cytoplasmic bridges in early spermatids of the rat: mechanisms of haploid gene product sharing. Mol. Biol. Cell 14, 2768–2780.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Vuillaumier, S. , Kaltenboeck, B. , Lecointre, G. , Lehn, P. , and Denamur, E. (1997). Phylogenetic analysis of cystic fibrosis transmembrane conductance regulator gene in mammalian species argues for the development of a rabbit model for cystic fibrosis. Mol. Biol. Evol. 14, 372–380.
PubMed |

Wheeler, M. B. , and Walters, E. M. (2001). Transgenic technology and applications in swine. Theriogenology 56, 1345–1369.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Yonash, N. , Leitner, G. , Waiman, R. , Heller, E. D. , and Cahaner, A. (1996). Genetic differences and heritability of antibody response to Escherichia coli vaccination in young broiler chicks. Poult. Sci. 75, 683–690.
PubMed |

Zeiher, B. G. , Eichwald, E. , Zabner, J. , Smith, J. J. , Puga, A. P. , McCray, P. B. , Capecchi, M. R. , Welsh, M. J. , and Thomas, K. R. (1995). A mouse model for the delta F508 allele of cystic fibrosis. J. Clin. Invest. 96, 2051–2064.
PubMed |