ARTICLE No3 REWPLANT-MADE PHARMACEUTICALS- AN ...

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Basini Jyothi et al/JITPS 2010, Vol.1 (1), 19-23

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ISSN:0975–8593
Review Article
Available online at www.itpsonline.netAvailable online at www.itpsonline.netAvailable online at www.itpsonline.netAvailable online at www.itpsonline.net

PLANT-MADE PHARMACEUTICALS- AN OVERVIEW
Basini Jyothi
1*
, Raja Shekar.A
1
, Satish.S
1
, Sabitha.P
1
, K.Ravindra Reddy
1

1*
P.R.R.M College of Pharmacy, Prakruthi nagar, 1-31/1, Utukur, Kadapa,
Andhra Pradesh, India- 516003
* Corresponding author E Mail: jyothi_811@yahoo.co.in
___________________________________________________________________________
Abstract
Plant-Made Pharmaceuticals (PMPs) are the agents that can be produced in the plants by the
genetic transformation and gene-expression methods in order to obtain therapeutic proteins
which can be used for the treatment of various diseases that can afflict hundreds of thousands
of people. The PMPs production involves less capital needs unlike the drugs manufactured by
the industries. This can achieve large scale production within short duration and meet the
patient needs effectively.
Keywords: Plant- made Pharmaceuticals, Genetic Transformation, Therapeutic Proteins.
___________________________________________________________________________

1. INTRODUCTION
Plant-Made Pharmaceuticals (PMPs) are
the result of an innovative application of
biotechnology, whereby plants are
genetically modified to produce new drugs
and biologics that can prevent or treat
diseases and save lives [1]. These are the
category of therapeutic agents (therapeutic
proteins) produced in live plants. In this
process, plants themselves become
‘factories’ that manufacture therapeutic
proteins. These proteins are then extracted,
refined and used as the Active
Pharmaceutical Ingredient (API) in many
medicines. Development and
commercialization of these products has
been regulated by the United States
Department of Agriculture (USDA),
Environmental Protection Agency (EPA),
Food Drug Administration (FDA) [2].
The use of transgenic plants to produce
pharmaceuticals will enable the
commercialization of life saving products.
This technology will allow the production
of drugs and biologics at a scale and cost
that might not be possible with other
systems. Beyond cost and scale, PMPs will
be produced by a process that is fully
sustainable because the plants and crops
used as raw materials are renewable
resources [1].
The Biotechnology Industry organization
(BIO) believes in the promise this
technology holds to treat and cure major
diseases that afflict hundreds of thousands
of people such as heart disease , allergies,
cancer, diabetes, Alzheimer’s and others.
2. THERAPEUTIC PROTEINS [3]
2.1 ANTIBODIES
Transgenic plants have been used for the
production of antibodies –directed against
dental caries, rheumatoid arthritis, E.coli
diarrhea, malaria, certain cancers etc.
Some of these have demonstrated
preventative or therapeutic value and are
currently in clinical trials. The most
advanced product to date is an anti-
streptococcus mutant’s secretary antibody
for the prevention of dental caries that is
currently in phase -II clinical trial. Plants
offer the only viable, large scale
production system for this antibody [4, 5].
2.2 VACCINES
Protein antigens from various pathogens
have been expressed in plants and used to
produce immune responses resulting in
protection against diseases in humans.
Plant derived vaccines have been
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produced against vibrio cholera,
enterotoxigenic E.coli, various viruses etc.
Insulin in plants produced a vaccine useful
for protection against insulin-dependent
auto immune diabetes mellitus.
2.3 OTHER PROTEINS
Expression in plants of milk protein such
as lactoferrin and beta casein may


Contribute the therapeutic values of these
proteins to other food products.
3. PRODUCTION OF PMPS
Advance in biotechnology have made it
possible to genetically enhance plants to
produce therapeutic proteins essential for
the production of a wide range of
pharmaceuticals such as monoclonal
antibodies, enzymes and blood proteins.
These plants are grown under highly
regulated conditions in confined growing
environments and are strictly regulated by
the U.S. Department of Agriculture
(USDA). After the plants are harvested,
they go through a series of processing
steps that extract, separate, purify and
package the therapeutic proteins. The
refined therapeutic properties are
ultimately used as the API in many life
saving medicines (Figure.1).

3.1 PROTEIN EXPRESSION SYSTEM
To achieve specific protein production in
plants, the DNA that encodes the desired
protein must be inserted into the plant
cells. This can be done as a stable
transformation when foreign DNA is
incorporated into the genome of the plant.
Alternately, a plant virus can be used to
direct expression [6] of a specific protein
without genetically modifying the host
plant.
3.2 PLANT TRANSFORMATION
SYSTEMS
Foreign genes may be inserted, or
transformed, into plants via a number of
methods. Stable transformation into the
nuclear genome is done primarily using
Agra bacterium mediated transformation
or particle bombardment methods [7]. In
each case, the DNA coding for the protein
of interest and an association promoter to
target its expression to a particular tissue
or developmental stage is integrated into
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the genome of the plant. Thus, when the
plant is propagated, each plant will
transmit this property to its progeny and
large numbers of plants containing the
transferred gene are readily generated.
3.3 VIRAL EXPRESSION SYSTEMS
A second method of engineering plant
protein expression is transduction, the use
of a recombinant plant virus [8] to deliver
genes into plant cells. The DNA coding for
the desired protein is engineered into the
genome of a plant virus that will infect a
host plant.
A crop of the host plants is grown to the
proper stage and is then inoculated with
the engineered virus. As the virus
replicates and spreads within the plant,
many copies of the desired DNA are
produced and high levels of protein
production are achieved in a short time.
The entire plant is then harvested to extract
the protein.
4. CONSUMER BENEFITS OF PMPs
PMPs production can also be made easily
expanded to provide large quantities if
demand for the drug increases.
Additionally, because plants are renewable
in nature and can produce pharmaceutical
proteins within a single growing season,
production can be quickly scaled up to
meet patient needs.
Production and cost advantages of plant
made pharmaceuticals can allow more
capital to be invested in research and
development of new therapeutics, giving
patients access to new drugs faster.
Immunex didn’t have the money to build a
large enough scale facility to manufacture
Enbrel in large enough quantities. This is
where transgenic plants could have an
advantage. If Enbrel were produced in
corn, they could have just planted more
acres, which would have been much less
expensive than building new, larger
facilities.
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5. PHARMACEUTICALS
PRODUCING CROPS
Crops that have been identified as good
potential sources for production of
pharmaceuticals include alfalfa, canola,
corn, potato, rice, safflower, soya beans
and tobacco [1].
6. DISEASES TREATED WITH
PMPs
Plants improved through the use of
biotechnology can produce the essential
building blocks (therapeutic proteins) for
innovative treatments for diseases such
as Alzheimer’s disease, Cancer, Chronic
obstructive pulmonary disease (COPD),
Crohn’s disease, Hepatitis C, HIV,
Rheumatoid arthritis, Obesity
7. PRODUCTION PRACTICES [3]
Unlike conventional crops, PMPs are
grown under a closed system that is
regulated by government agencies and
controlled completely by the technology
provider and manufacturer. CBER
(Center for Biologics Evaluation and
Research) regulates the manufacturing
Of PMPs and considers fields of
pharmaceutical crops to be ‘factories’.
The technology provides must obtain a
permit from APHIS (Animal and Plant
Health Inspection Service) to produce
the PMPs and contracts in advance with
farmers to grow the crop. It is the
responsibility of technology providers
and manufactures to document the
required crop management practices and
to ensure that Good Agricultural
Practices (GAP) and Good
Manufacturing Practices (GMP) are
followed. GMP producers include
standards for quality management,
personal training, building and facilities,
process equipment, documentation and
records, materials management,
production and in-process controls,
packaging and labeling for transport,
storage and distribution, laboratory
controls, and process validation.
8. APPLICATION OF PMPs
Pharmaceuticals produced from biotech
plants are a new application of
biotechnology that turns plants into
‘factories’ that produce therapeutic
proteins used in biopharmaceuticals.
Plants may after a cost effective,
sustainable and faster source of
medicines for patients and provide
access to new treatments which would
otherwise be out of reach. In January
2005, market research firm frost and
Sullivan predicted that the PMPs market
could realize revenues of $98.2 billion
by 2011.
8.1 Plant-made vaccines
8.2 Plant made proteins in electrolyte
replacement: Ventria has developed an
electrolyte solution that includes lactiva
(lactoferrin) and lysomin (lysozyme),
two proteins naturally found in breast
milk, which are produced in rice.
8.3 Plants used to control the diabetes
epidemic.
In July 2006, Sem Biosys announced
that it can produce over one kilogram of
insulin per acre of protein-producing
biotech safflower. This is enough to
supply 2500 patients for one year of
treatment each.
9. PMPs TECHNOLOGIES
The need, once again for the PMP
industry to convince the pharmaceutical
community that PMPs can become an
established route of large scale
production, brings us conveniently to a
short overview of PMPs technologies,
their capabilities, characteristics,
strengths and weaknesses[9] (Table.1).
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10. PMPs OPPURTUNITIES TODAY [9]
The basic philosophy of the PMPs
opportunity today can be stated in the
following way;
10.1 There is a substantial, and
increasing, worldwide demand for
protein pharmaceuticals and therapeutics
10.2 Specialized plant-based gene
expression technologies are ready to
provide an alternative manufacturing
platform that can help meet the demand
and thus overcome the perceived
bottleneck in protein production [10].
Taken together, these situations make a
strong case for commercial development
of PMPs.
11. CONCLUSION
PMPs offer great promise to prevent,
treat and cure major diseases that affect
hundreds of thousands of people. This
document has provided our
understanding of the relevant regulatory
process and stated the industry practices
that will be used to comply with that
process. It is our firm belief that the
benefits of plant made pharmaceuticals
out weigh the risks incurred in their
production and that guidance issued
under the existing regulatory framework,
together with industry practices outlined
in this document, will ensure that the
concomitant risk is minimal.
12. REFERENCES
[1] Biotechnology Industry Organization.
Reference Document for Confinement
and Development of Plant Made
Pharmaceuticals in the United States,
May 17, 2002.
[2] USDA APHIS (Animal and Plant
Health Inspection Service) 2002.
Summary of the confinement
measures for organisms being field
tested in 2002.
[3] BRUCE R. THOMAS., ALLEN VAN
DEYNZE., KENT J. BRADFORD.
Production of therapeutic proteins in
plants, Agricultural Biotechnology in
California series, Publication 8078.
[4] Gavilondo, J.V and Larrick,J.W., 2000.
Antibody engineering at the
millennium. Biotechniques., 29,
128-145.
[5] Larrick, J.W. and Thomas, D.W., 2001.
Producing proteins in transgenic plants
and animals., Cur. Opinion in Biotech.
12, 411-418.
[6] Lacomme, C., 2001. Plant viruses as
gene expression vectors. In: Genetically
Engineered Viruses (Ring CJA and
Blair ED Eds.). Oxford: BIOS Scientific
Publishers Ltd.., 59–99.
[7] Suslow, T.V., Thomas, B.R., Bradford.
K.J., 2002. Biotechnology provides new
tools for planting. Okaland, University
of California Division of Agriculture
and Natural Resources, Publication
8073.
[8] Bardor, M.L., Faye, Lerouge,P.,1999.
Analysis of N-glycosylation of
recombinant glycoproteins produced in
transgenic plants. Trends in plant Sci, 4,
376-380.
[9] Maelor Davies, H., Plant Made
Pharmaceuticals. AN Overview and
Update, University of Kentucky,
Lexington, ky.
[10] Garber, K., 2001 Biotech industry faces
new bottleneck. Nature Biotechnol. 19,
184–185.