Biomedical Engineering Reference
In-Depth Information
Table 14.5
A selection of pharmaceutical recombinant human proteins expressed in plant systems.
Species
Recombinant human product
Reference
Tobacco, sunflower (plants)
Growth hormone
Barta
et al.
1986
Tobacco, potato (plants)
Serum albumin
Sijmons
et al.
1990
Tobacco (plants)
Epidermal growth factor
Higo
et al.
1993
Rice (plants)
a
-Interferon
Zhu
et al.
1994
Tobacco (cell culture)
Erythropoietin
Matsumoto
et al.
1995
Tobacco (plants)
Haemoglobin
Dieryck
et al.
1997
Tobacco (cell culture)
Interleukins-2 and 4
Magnuson
et al.
1998
Tobacco (root culture)
Placental alkaline phosphatase
Borisjuk
et al.
1999
Rice (cell culture)
a
1
-Antitrypsin
Terashima
et al.
1999
Tobacco (seeds)
Growth hormone
Leite
et al.
2000
Tobacco (chloroplasts)
Growth hormone
Staub
et al.
2000
in soybean (Zeitlin
et al.
1998). Even secretory IgA
(sIgA) antibodies, which have four separate poly-
peptide components, have been successfully expressed
in plants. This experiment involved the generation
of four separate transgenic tobacco lines, each
expressing a single component, and the sequential
crossing of these lines to generate plants in which
all four transgenes were stacked (Ma
et al.
1995).
Plants producing recombinant sIgA against the oral
pathogen
Streptococcus mutans
have been generated
(Ma
et al.
1998), and these plant-derived antibodies
('plantibodies') have recently been commercially
produced as the drug CaroRx
TM
, marketed by Planet
Biotechnology Inc. A number of other biotechnology
companies are bringing antibody-expressing trans-
genic plants into commercial production (see Fischer
& Emans 2000).
2001). These genes will then become targets for new
small-molecule drugs. Already drugs have been
developed based on such genotype-phenotype
correlations. For example, Wettereau
et al.
(1998)
identified a molecule that normalizes atherogenic
lipoprotein levels caused by a genetic deletion of a
microsomal triglyceride transfer protein.
The identification of genetic changes associated
with particular disease phenotypes offers a number
of novel approaches to the development of therapies.
As well as using such changes as novel targets for
small-molecule drug design, there is an opportunity
to use the techniques described in Chapter 11 to gen-
erate animals with the exact same genetic defect and
which can be used as models to test new drug candid-
ates (
disease modelling
). Furthermore, where drugs
cannot be developed to treat a particular disorder,
there might be an opportunity to correct the disease
by further modification to the genome (
gene therapy
).
Finally, it is likely that, in the near future, transgenic
animals could be used to provide healthy organs for
humans requiring transplants (
xenotransplantation
)
(Box 14.2). These topics are discussed in more detail
below.
The impact of genomics
Many of the drugs currently on the market treat the
symptoms
of the disease rather than the
cause
of the
disease. This is analogous to reversing a mutant
phenotype by selecting a mutation at a second
site. Not surprisingly, many of these drugs have
side-effects quite separate from those (e.g. toxicity)
caused by their metabolism. Now that the first drafts
of the human genome sequence are available, it
will be possible to convert disease phenotypes into
nucleotide changes in specific genes (Bailey
et al.
Transgenic animals as models
of human disease
Mammals have been used as models for human
disease for many years, since they can be exploited to
