Rice as bioreactors : Oral delivery system for vaccine antigens, immunotherapy and therapeutic proteins are recent advances.
6 Streatfield SJ et al., 2003
7 Production platform Cont… Ventria Bioscience (US Based Company) : Two rice-derived proteins
Human lactoferrin and lysozyme
Have received regulatory approvals, and lactoferrin has already been marketed in bulk for bioprocessing.
Production platforms (Cont.…) Legumes:
Soybean and pea: Seeds have high protein content (20–40%).
Both self-pollinating plants & low risk of contamination.
Soybean : Express a humanized antibody against Herpes simplex virus. Bovine casein, and a Human growth hormone. (Russell et al., 2005)
Safflower and rapeseed : Rich in seed oil & inexpensive downstream.
Safflower : High protein yield, Low acreage, and Self-pollinating.
Oilseed-derived protein: Commercial production of Hirudin, an anti-coagulant for treatment of thrombosis in rapeseed by SemBioSys(Bootheet al., 1997)
Where they are produced? Shown are various Intracellular organelles or Extracellular spaces (ES) that can be used to store the recombinant proteins expressed in a plant bioreactor. Targeting strategies in plant bioreactors. G- Golgi; PSV- Protein storage vacuole; OB - Oil body; C- Chloroplast; ES- Extracellular space; PVC - Prevacuolar compartment. 9
Products obtained… Plants genetically engineered to make products that are not of plant origin Products:
10 Tree depicting biotechnological advances using plants as bioreactors Source: www.plantbioreactor.co.in/images/00_112.jpg
Products : Plant as bioreactor Vaccine antigens:
It is an antigenic preparation : Immunity against a disease.
Recent Development : “Edible Vaccines” now more popular as “Plant Vaccines”
From Seeds, freeze-dried fruits and leaves: powder form vaccines are produced.
Antigenic determinantsfor Pathogens causing diseases have been produced from plants.(Diarrhea, anthrax, rabies, cancer, HIV, tuberculosis etc)
Antigens like Insulin, rotavirus enterotoxin, anthrax lethal factor, HIV antigen, foot and mouth disease virus antigen, heat stable toxin have been produced in plants as a fusion partner of CTB or LTB.
11 http://www.dowagro.com/uk/media/General/20061017.htm, Khandelwalet al., 2003; Sharma et al., 2004, Streatfield and Howard, 2003, Tiwariet al., 2009 and Youm et al., 2008.
Products : Plant as bioreactor(Cont.…) Therapeutic products:
Diagnostic proteins (antibodies and enzymes), replacement proteins, immune system stimulator/suppressants, biopolymers and adhesive proteins are produced in plants.
Production of immunoglobulin fragments and their assembly in plants –reported in tobacco.
Recently known as “plantibodies” – immunochromatography or medical therapy.
12 Schillberget al., 1999, Ma et al., 2003, Goldstein and Thomas, 2004
Products : Plant as bioreactor Therapeutic products:
Many form of recombinants antibodies are produced in plants.
Sub cellular destination - high level expression.
Further research is concentrated on Humanizing the Plant N-glycans.
13 Schillberget al., 1999, Ma et al., 2003, Goldstein and Thomas, 2004
Products : Plant as bioreactor(Cont.…) Nutritional components:
It can provide most of the nutrients required in the human diet.
Plant have been engineered to increase accumulation of:
β-carotene(Naqvi et al., 2009), Lycopene(Fraser et al., 2002), Flavonoid(Butelli et al., 2008), Nutraceuticals (Kang et al., 2009), Fatty acid (Hoffmann et al., 2008), Vitamins (Nunes et al., 2009), Minerals(Lee & An, 2009) & Carbohydrates (Regina et al., 2006). Biodegradable plastics:
Polyhydroxyalkanoates: biodegradable polymers which occur naturally in plants.
Plant was engineered to produce PHAs or PHBs in the various plant cell compartments.
When PHB expression targeted to cytoplasm, accumulation level was low.
Expression was increased by targeting plastids, (40% of dry weight was obtained).
Products : Plant as bioreactor(Cont.…) Industrial products:
First produced protein : Human growth hormones in tobacco.
Most expensive Drug – hGC (Human glucocerebrosidase) in tobacco (Kaiser 2008).
hST (Human somatotropin) was produced in tobacco (Staubet al. 2000).
Which treats : Turner syndrome, Chronical renal failure & Dwarfism in Children.
rHLF (Recombinant human lactoferrin) : Produced from dehusked rice grain(Nandi et al., 2002). Which is identical to native HLF.
Synthetic fiber: Produced from Potato and tobacco. (Schelleret al., 2001)
More and more uses of plant bioreactors are coming up these days.
Plant bioreactors : Investigated for making enzymes (Suitable for Food).
Another use of plants is to make genetically engineered plants that can produce seeds which can function as a delivery mechanism for various industrial enzymes.
As you can see these processes go far beyond the application of biotechnology in traditional agriculture, and so today, transgenic plants can produce on a mass scale proteins for agricultural, veterinary and pharmaceutical use.
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