A brief introduction of medicine we can produce in plants by high throughput techniques.

1. Production of
biopharmaceuticals in plants
By
Muhammad Adil Salim

2. The production of pharmaceuticals in plants
• recombinant human insulin from bacteria, was produced
in 1982
• genetically modified plant in 1984
• human growth hormone fusion protein
• Interferon- class of cytokines effective vs viral infections
• monoclonal antibodies
• serum albumin
• pharmaceutical production in plants can be described in three
broad categories of therapeutics:
• antibodies,
• vaccines, and
• other therapeutics.

3. Antibodies
Monoclonal antibodies (mAbs) : therapeutic and diagnostic purposes
Traditional therapeutic monoclonal antibodies have been derived from mice
identified by the human immune system as foreign
limiting the utility of these antibodies for therapeutic use,
recombinant technologies have allowed murine antibodies to be replaced
with
partially humanized or chimeric antibodies.

4. Plants now have potential to produce mAbs, referred as ‘plantibodies’.
Tobacco plants: used extensively for antibody expression systems.
other plants :potatoes
soybeans
alfalfa
rice and
corn
Antibody formats can be full-size, Fab fragments, single-chain antibody
fragments, bi-specific scFv fragments, membrane anchored scFv, or
chimeric antibodies.

5. Plant cells, unlike mammalian cell expression systems, can express recombinant
secretory IgA (sIgA ).
sIgA is a complex multi-subunit antibody that may be useful in topical immunotherapy
(tobacco)
producing humanized antibodies against herpes simplex virus-2 . (Soya bean)
GE corn reportedly is capable of producing human antibodies at yields of up to a kg
per acre,
to preserve antibody function through five years of storage under ordinary conditions.

6. Recombinant antibodies expressed in
transgenic plants
Antibodies binding including:
binding to pathogenic organisms,
binding to serum or body fluid effector proteins (e.g. interleukins),
or binding to a cellular receptor site to up- or down-regulate
receptor function.
four antibodies expressed in plants :
1. IgG/IgA antibody effective against a surface antigen of
Streptococcus mutans
effective against dental caries

7. 2.humanized anti-herpes simplex virus (HSV), :
preventing the transmission of vaginal HSV-2 in animals
3. Rice and wheat expression systems can produce antibodies
against carcinoembryonic antigen .
4. treatment of lymphoma
No ‘plantibodies’ have currently
reached the commercialized
stage

8. Recombinant antibodies expressed in transgenic
plants
Year Format Antibody/Antigen Plant organ Cellular location Transformed
species
1989 IgG1
Phosphonate ester Leaf
1990 IgMNP hapten
1992 scFv
Phytochrome
1996 scFv
Cutinase
Leaf
Leaf
Leaf
Leaf
1997 scFv Abscisic acid
Seed
Tuber
Tobacco
ER/chloroplast Tobacco
1997 scFv Abscisic acid
1998 scFv Oxazolone
ER
Cytosol
ER
ER
ER
ER
Tobacco
Tobacco
Tobacco
Tobacco
Potato

9. Vaccines
low production cost,
increased safety,
stability,
versatility, and efficacy.
grown locally where needed, avoiding storage and transportation costs.
Relevant antigens are naturally stored in plant tissue,
that refrigeration will not be needed to preserve vaccine efficacy
free of contamination with mammalian viruses

10. Transgenic potatoes ….diarrhoea.
‘edible vaccines’ are under development for :
rabies,
foot and mouth disease(veterinary)
cholera, and autoimmune diabetes.
Transgenic lupin and lettuce plants can express hepatitis B
surface antigen.
Efforts are underway to develop an ‘edible vaccine’ against
the measles virus using the tobacco plant
.

11. Recombinant vaccines expressed in plants
The plant species to be used for the production and delivery of an oral vaccine are:.
alfalfa, apple, banana, cabbage, canola, carrots, cauliflower, cucumber, grape,
lettuce,
maize, melon, papaya, pea, peanut, plum, potato, rice,, soybean, squash, strawberry,
sugar beet, sugarcane, sunflower, sweet potato, tomato, walnut, and wheat
banana the best choice for infants.
component of many diets
consumed uncooked,
eliminating the possibility of protein denaturation due to high temperatures

12. Recombinant vaccines expressed in plants
1992
Hepatitis virus B surface antigen
Tobacco
1995
Rabies virus glycoprotein
Tomato
1995
Escherichia coli heat-labile
1996
enterotoxinTobacco
Norwalk virus capsid protein
Tobacco Potato
1997 Diabetes-associated autoantigen
TobaccoPotato
1997 Hepatitis B surface proteins
Potato
1998 Human insulin-Cholera toxin B subunit fusion protein Potato
1999 Foot and mouth disease virus VP1 structural protein Alfalfa
1999 Hepatitis B virus surface antigen
Yellow lupin, lettuce
1999 Human cytomegalovirus glycoprotein B
1999 Dental caries (S. mutans)
1999 Diabetes-associated autoantigen
2002 Respiratory syncytial virus
Tobacco
Tobacco
TobaccoCarrot
Tomato

13. Other therapeutic agents
A wide variety of other therapeutic agents have been derived from plants :
hormones (somatotropin)
enzymes,
interleukins
interferons (IFN)
and human serum albumin

14. Thanks and Questions ??
Muhammad Adil
adilsaleem105@gmail.com
@adil_salim