Molecular Pharming Flashcards
(15 cards)
Why is recombinant protein pharmaceuticals in plants a good option?
More potential for greater efficacy and lower side effects (compared to small organic molecules)
Why are CHO cell lines used but maybe not the most beneficial?
CHO (Chinese hamster ovary) cell lines are most used because they are mammalian cells, and post translation modifications are more likely to be human like.
BUT
Expensive, hard to scale up, can be contaminated with animal viruses and proteins.
What are the opportunities for biopharmaceuticals in GM plants?
- Relatively simple small scale trials, scaled up, large scale biomass production possible
- Low infrastructure costs
- No contamination with animal viruses and proteins
- Eukaryotic
Many human proteins have been successfully expressed in plants but at low levels.
What are some examples of molecular pharming setbacks?
- 2002, Prodigene incident: Leftover GM corn harvested with subsequent soybean crop, fined $250,000, clean up costed $3 mill
- Iowa: GM crops cross pollinated with neighbouring field
What was the first plant bipharm to get FDA approved?
Elelyso, 2012
To treat Gaucher disease
Recombinant glucocerebrosidase produced in carrot cell bioreactors
Cheaper than existing CHO system
What do plants producing monoclonal antibodies express?
Single chain recombinant anti-gen binding antibody fragments
Not as effective, but easier to express
What is an example of a plant expressing monoclonal antibodies?
1989, mouse LgVH and VL genes were introduced separately into tobacco
The progeny of the cross produced functional antibodies, but transgene design needed to be optimised
How were plants used for the Ebola virus vaccine?
Zmapp
3 monoclonal antibodies transiently expressed in plants
High yields
Superior potency than CHO
Treated 7 patients
What is transient transformation?
Introduction of foreign genetic material into a cell
Short term expression
Genetic material not passed down
What are the advantages and disadvantages of transient expression?
ADVANTAGES:
- High protein levels can be achieved
- Quick and easy
- Transgenic material easily contained
- No transgenic seed/pollen
DISADVANTAGES:
- Difficult to control protein levels
- Cannot retain seed stock
- Only works well for small proteins
What are the benefits of obtaining vaccines from plants?
- Cost effective production
- Rapidly and cheaply produce complex proteins
- Potential lack of need for refrigeration
- No human pathogen contaminants
- Good for oral vaccines
Explain the plant vaccine for Newcastle disease
Vaccine: Newcastle disease virus HN
- Disease affects poultry
- Expressed hemagglutinin-neuraminidase protein antigen in tobacco cell suspension
- Subcutaneous
- USDA approved, but not commercialised
Explain the potential Hepatitis plant vaccine
- Expressed Hep B surface antigen in potatoes
- Fed to mice, similar immune response to vaccine
- BUT humans do not eat raw potatoes, proteins would be denatured while cooking
Explain the COVID19 plant vaccine
- Spike glycoprotein transiently expressed in tobacco
- Mimics the surface of SARS-COV2 but is non-infectious and non-replicating (no viral RNA)
- Licensed for use in Canada, but shut down by owners in 2023
What are the challenges of vaccines from plants?
- Expression levels in fruit are not all the same, difficult to dose
- Downstream processing can be complex
- Potential contamination of food chain
- Potential for oral tolerance
