have been generated which secrete biopharmaceuticals in their milk (Wright
et al. 1991 ). The choice of species used is based on subtle differences in post-
translational modification, the quantity of product that the market would require
and the time taken to expand the transgenic colony to the point that it would
satisfy the quantity requirement. Products currently under consideration are recom-
binant human antithrombin III, human inhibitorC1, human fibrinogen, human
albumin, humana-antitrypsin, as well as potential protein vaccines including
rotavirus VP2/VP6 and malaria antigen (Houdebine 2009 ).
Kind and Schnieke have recently examined both the history and the likely future
of animal pharming (Kind and Schnieke 2008 ). In the last 20 years cell based
manufacturing has produced a series of highly profitable proteins, such as Epogen
(recombinant erythropoietin) and Enbrel (recombinant anti tumour necrosis factor)
whereas the pharming industry has only had one product approved, recombinant
human antithrombin III (ATryn) marketed by GTC Biotherapeutics. Approval was
granted in Europe in August 2006 and in the USA in February 2009. The contrast
between the successes of the cell based manufacturing and the pharming industries
is somewhat surprising as pharming would appear to have cost advantages. It has
been estimated that cell-based manufacturing is 3–30 times more expensive than
pharming and it also requires a very large initial capital outlay to build a culture
facility of sufficient size to produce a protein on the scale necessary for regular
therapeutic use (Farid 2007 ).
So why has animal pharming struggled to compete? A significant problem was
that the early projects used microinjection transgenic technology and the transgenes
proved unstable in a number of cases. Such variation was unacceptable to the
regulatory authorities. This problem can now be addressed by specific gene target-
ing, using nuclear transfer. A possible growth area for the future will be the
generation of transgenic cattle that can produce humanised polyclonal antibodies.
Such antibodies would be of great benefit in treating venoms and pathogens that
mutate rapidly and would be a large market that could only be provided by
pharming (Kind and Schnieke 2008 ).
6 Gene Therapy for Diseases of Companion and Farm Animals
As noted in the previous sections, transgenic animals, which are genetically mod-
ified at the level of the germline and so transmit the genetic modification to
subsequent generations, have a large number of uses in pharmacology. Genetic
modification can also be performed on somatic tissues, treating just the individual.
Somatic gene transfer requires a system (vector) to transfer the genetic material into
the cell. There are two broad classes of vectors, viral and non-viral. The former are
derived from a range of viruses and have been engineered to retain the highly
efficient mechanisms for delivering genetic material into the target cell while
preventing replication by deleting some or all of the viral genes. Viral vectors
220 D.J. Wells