M.B.D Article Flashcards
Understand key ideas in this article
DARPA goals
1) Synthesizing biologics on demand to eliminate the need for refrigerating drugs. (Making insulin & other biologics on the spot)
2) Reduce the need to stockpile biologics for chemical, biological, radiological or nuclear attacks.
3) more drugs made on the spot in response to epidemics or attacks
Biologics
Normally synthesized in large batches in large scale reactors, thousands of liters, by cells engineered to produce desired proteins.
Cells engineered to produce desired proteins
Escherichia coli, yeast, chinese hamster ovary (CHO)
E.coli (for producing proteins)
The cells must be lysed to recover the proteins
Yeast or CHO (for producing proteins))
Cells secrete the proteins, which simplifies purification
MIT system
1) System that can be easily switched from producing one molecule to another
2) Requires to understand well the biology of the host cell that produces the products
3) InSCyT
InSCyT
1) Uses pichia pastor is yeast cells (small genome)
2) Produces various drugs in bench top manufacturing system within 24 hours
3) Has all components of a conventional biomanufacturing at smaller scales
4) 3 modules (production, purification, and formulation module)
5) can produce end-to-end production of hundreds to thousands of doses of protein biologics in about 3 days
6) can be used to replace biopharmaceutical stockpiles
Pischia pastoris
1) Small inexpensive genome
2) Allows to think about tuning the host to make molecules of it rest with precision
3) yeast is quickly adapted to make new proteins w/ sequencing and genome tools
4) Allows to predict what proteins from host cells might contaminate their biological products
InSCyT production module
Here fermentation takes place
InSCyT purification module
Cell culture medium from module w/ protein product flows through tubing to a chromatography system here
InSCyT Formulation module
Purified protein is filtered
Bio-MOD (free cell system)
1) works without cells, uses freeze-dried extracts from CHO cells (gene transcription and translation)
2) fits in a suit case
3) single use protein production and purification modules
4) I am Speed
5) refrigeration is not needed during transportation
6) Freeze-dried cells like powdered milk (just add buffer and DNA-4-6hrs protein product produced
7) can use cell from human blood as a source
8) can make vaccine at point of care
Cons
Only for making small amounts of proteins
More purification required for cell debris
Cell free system bundy e.coli strain
Lifesaving protein therapeutics for abundant/common bacteria
Better for producing modest quantities in areas of limited resources
(Can be used to engineer non-natural amino acids to proteins) or make protains toxic to cells
Made cytokines, growth factkr, and peptides that degrade cellular systems
Cons:
Can use same expression system for multiple new products
Not suitable to produce sizable quantities
