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Molecular Pharming of
Pharmaceutical and Proteins.
Agricultural Biotechnology (EAG 311 – 2)
What is molecular pharming?
Refers to the production of pharmaceutically
valuable compounds from plants
Use whole organisms , organs , tissues, cells, cell
cultures as bio reactors for the commercially
valuable products via recombinant DNA technique.
Production systems in molecular
• Plant viruses
• Transgenic Plants
• Animal Cell Cultures
• Transgenic Animals
1. Production of vaccines
Plant vaccines are composed of antigenic proteins and
do not contain pathogenic genes.
Appropriate plant parts containing antigen can be fed to
humans to bring about immunization.
no purification required
no hazards associated with injections
Protein in spinach
Pig vaccine in corn
Human vaccine for hepatitus B in potato
• Plants were transformed with genes encoding
E.coli heat liable enterotoxin (LT-B) subunit.
• •Trangenic potatoes induce production of
serum and secretory antibodies in mice.
• •Transgenic potato with CT-B gene of Vibrio
cholerae was shown to be efficacious in mice.
• Co-expression of mutant cholera toxin subunit
A (CT-A) and LT-B in crop seed has been
shown to be effective.(Arakawa,1997)
Hepatitis B vaccine
• HBsAg has been introduced into tobacco plants
using CaMV vector
• •HBsAg was produced to 0.01% of total soluble
• •Tobacco derived HBsAg was present as 22nm
• •Successful parenteral immunization in mice
• •Cholera toxin,bacterial endotoxin can be used
• Transgenic tobacco expressing MV-H antigen
(measles virus haemagglutinin from
Edmonston strain) was produced by
• •Mice fed with transgenic tobacco could
attain antibody titers five times.
• •Transgenic rice, lettuce against measles are
also being developed.
• •Can be given with CT-B (adjuvant
• Human growth hormone, or somatotropin could
be produced in tobacco through plastid
• •Chloroplasts were shown to accumulate soluble
active and disulfide-bonded somatotropin.
• •High levels of somatotropin protein
accumulation within tobacco chloroplasts was
achieved by driving expression of the gene from
the plastid psbA promoter.
• diabetes is an autoimmune disease in which the
body’s immune system attacks and destroys insulin
and insulin-producing beta cells in the pancreas.
• developed genetically engineering tobacco plants
with the insulin gene it successful in mice
• It has been tried in lettuce also. Plant cell walls
made of cellulose initially prevent insulin from
• When the plant cells containing insulin reach the
intestine, bacteria living there begin to slowly
break down the cell walls and gradually release
insulin into the bloodstream.
3. Production of INTERFERONS
A kind of protein that have the ability to interfere with viral growth.
Interferons were discovered in 1957 by Alick Isaacs and Jean
Tobacco plants were transformed with the human gene for
interferon-β (IFN-β) using Agrobacterium tumifaciens binary vector.
Human interferon-β expressed in rice,turnip and tobacco are used
in the treatment of Hepatitis B and Hepatitis C.
4. Production of PLANTBODIES
Plantbodies are humanized monoclonal antibodies.
The term "plantibodies" was created to describe the
products of plants that have been genetically engineered
to express antibodies and antibody fragments
Free from potential contamination of mammalian viruses
First functional antibody to be expressed was IgG6D4
specific for a synthetic phosphanate ester P3.
5. Cancer therapy
• Plants can make monoclonal antibodies for
cancer therapy in sufficient quantities.
• Soybean has been genetically engineered to
make monoclonal antibody (BR-96) as a vehicle
for targeting doxorubicin for breast, ovarian,
colon and lung tumors.
Risks and Concerns
• Environment contamination
• Food supply contamination
• Health safety concerns
Non-target organ responses
• The production of PDP may provide a cheaper and
better alternative source of medicines for both developed
and developing countries.
• The latter will benefit the most because of reduced
costs of drug production, the possibility of large scale
. • Locally grown crops can be developed for PDPs, which
could make them more practical and economical.
• However, there are risks, concerns, and other issues
which need to be addressed
Examples of Current Research
Genetically engineered Arabidopsis plants can sequester arsenic
from the soil. (Dhankher et al. 2002 Nature Biotechnology)
Immunogenicity in human of an edible vaccine for hepatitis B
(Thanavala et al., 2005. PExpression of single-chain antibodies in
transgenic plants. (Galeffi et al., 2005 VaccineNAS)
Plant based HIV-1 vaccine candidate: Tat protein produced in
spinach. (Karasev et al. 2005 Vaccine)