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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
pharming
• Yeast
• Bacteria
• Plant viruses
• Transgenic Plants
• Animal Cell Cultures
• Transgenic Animals
Molecular pharming process.
Plant Made Pharmaceuticals
• Plantibodies
• Vaccines / Plantigens
• Interferons
• Blood clotting factors
• Anticoagulant
• Hormones
• Enzymes
• Secondary metabolites
• Other proteins
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.
Advantages:
Administered Directly
no purification required
no hazards associated with injections
Examples
Protein in spinach
Pig vaccine in corn
Human vaccine for hepatitus B in potato
Cholera vaccines
• 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
leaf protein
• •Tobacco derived HBsAg was present as 22nm
virus particles
• •Successful parenteral immunization in mice
• •Cholera toxin,bacterial endotoxin can be used
as adjuvants
Measles vaccines
• Transgenic tobacco expressing MV-H antigen
(measles virus haemagglutinin from
Edmonston strain) was produced by
Agrobacteriummediated transformation.
• •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
2. Production of hormones .
SOMATOTROPIN
• Human growth hormone, or somatotropin could
be produced in tobacco through plastid
transformation.
• •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.
INSULIN
• 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
degrading.
• 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
Lindenmann
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
Side-effects
Allergenicity
CONCLUSION
• 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
production
. • 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)
Reference
 Molecular Pharming,
https://vttindustrialbiotechnology.com/tag/molec
ular-pharming, 2016/05/21
 Molecular Pharming and Biopharmaceuticals
http://www.isaaa.org/resources/publications/poc
ketk/26/default.asp, 2016/05/21
THANK YOU!!!!!!

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Molecular pharming

  • 1. Molecular Pharming of Pharmaceutical and Proteins. Agricultural Biotechnology (EAG 311 – 2)
  • 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.
  • 3. Production systems in molecular pharming • Yeast • Bacteria • Plant viruses • Transgenic Plants • Animal Cell Cultures • Transgenic Animals
  • 5. Plant Made Pharmaceuticals • Plantibodies • Vaccines / Plantigens • Interferons • Blood clotting factors • Anticoagulant • Hormones • Enzymes • Secondary metabolites • Other proteins
  • 6.
  • 7. 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. Advantages: Administered Directly no purification required no hazards associated with injections Examples Protein in spinach Pig vaccine in corn Human vaccine for hepatitus B in potato
  • 8. Cholera vaccines • 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)
  • 9. Hepatitis B vaccine • HBsAg has been introduced into tobacco plants using CaMV vector • •HBsAg was produced to 0.01% of total soluble leaf protein • •Tobacco derived HBsAg was present as 22nm virus particles • •Successful parenteral immunization in mice • •Cholera toxin,bacterial endotoxin can be used as adjuvants
  • 10. Measles vaccines • Transgenic tobacco expressing MV-H antigen (measles virus haemagglutinin from Edmonston strain) was produced by Agrobacteriummediated transformation. • •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
  • 11. 2. Production of hormones .
  • 12. SOMATOTROPIN • Human growth hormone, or somatotropin could be produced in tobacco through plastid transformation. • •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.
  • 13. INSULIN • 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 degrading. • 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.
  • 14. 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 Lindenmann 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. .
  • 15. 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.
  • 16. 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.
  • 17. Risks and Concerns • Environment contamination • Food supply contamination • Health safety concerns Non-target organ responses Side-effects Allergenicity
  • 18. CONCLUSION • 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 production . • 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
  • 19. 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)
  • 20. Reference  Molecular Pharming, https://vttindustrialbiotechnology.com/tag/molec ular-pharming, 2016/05/21  Molecular Pharming and Biopharmaceuticals http://www.isaaa.org/resources/publications/poc ketk/26/default.asp, 2016/05/21