Title:Molecular Farming of Pharmaceutical Proteins Using Plant Suspension Cell and Tissue Cultures
Volume: 19
Issue: 31
Author(s): Stefan Schillberg, Nicole Raven, Rainer Fischer, Richard M. Twyman and Andreas Schiermeyer
Affiliation:
Keywords:
bioreactor, downstream processing, fermentation, recombinant proteins.
Abstract: Plants have been used for more than 20 years to produce recombinant proteins but only recently has the focus shifted away
from proof-of-principle studies (i.e. is my protein expressed and is it functional?) to a serious consideration of the requirements for sustainable
productivity and the regulatory approval of pharmaceutical products (i.e. is my protein safe, is it efficacious, and does the product
and process comply with regulatory guidelines?). In this context, plant tissue and cell suspension cultures are ideal production platforms
whose potential has been demonstrated using diverse pharmaceutical proteins. Typically, cell/tissue cultures are grown in containment
under defined conditions, allowing process controls to regulate growth and product formation, thus ensuring regulatory compliance.
Recombinant proteins can also be secreted to the culture medium, facilitating recovery and subsequent purification because cells contain
most of the contaminating proteins and can be removed from the culture broth. Downstream processing costs are therefore lower compared
to whole plant systems, balancing the higher costs of the fermentation equipment. In this article, we compare different approaches
for the production of valuable proteins in plant cell suspension and tissue cultures, describing the advantages and disadvantages as well as
challenges that must be overcome to make this platform commercially viable. We also present novel strategies for system and process optimization,
helping to increase yields and scalability.
