-210 Nottingham - Nottingham eTheses - The University of Nottingham

gene-targeting via somatic cell cloning allows the function of specific porcine genes
to be addressed, e. g. al, 3-galactosyltransferase (al, 3GT) allele knockouts (Lai et al.,
2002a; Dai et al., 2002; Phelps et al., 2003; Kolber-Simonds et al., 2004).
1.2.4.2 Medical applications
Cloned genetically modified pigs offers a new bioreactor for the production of
pharmaceutical proteins. This requires the adaptation of transgenesis. The early
method was to add function to animals by injecting the DNA encoding a gene into the
pronucleus of a zygote e. g. human protein C (Velander et al., 1992). This method has
limitations like inefficient integration of the required gene into the genome (Campbell,
2002a). Gene-targeting of donor cells followed by SCNT can introduce more precise,
site-specific integration of the gene of interest.
Pigs have already become popular as models for cardiovascular disease, cutaneous
pharmacology and toxicology, lipoprotein metabolism, and pathobiology of intestinal
transport, injury and repair (Prather, 2002). Porcine transgenic models have been
produced for the studies of omega-3 (n-3) fatty acids (Lai et al., 2006) and cystic
fibrosis (Rogers et al., 2008).
The inadequate supply of human organs/tissues for allotransplantation and the use of
immunosuppressive drugs to avoid rejection following allotransplantation have led to
the consideration of animals as organ donors. In particular, the pig appears to be a
suitable source of transplantable tissues for the following reasons: (1) Pigs are
physiologically and anatomically similar to human and the size of porcine organs is
close to those of human; (2) Pigs are litter bearing and cheaper than primates; (3) Pigs
can be genetically modified, which has not yet been achieved in primates.
Immunological rejection and pathogens like porcine endogenous retrovirus (PERV;
Patience et al., 1997) are the major barriers to progress in pig-to-human organ
transplantation.
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