Conventional methods for protein expression rely on bacteria, yeast, plant, or mammalian cell lines. Many proteins, however, cannot be manufactured in these systems, including those with novel chemical modifications such as non-natural amino acids.
Sutro Biopharma says its open cell-free synthesis (OCFS) method rapidly makes proteins that cannot be produced by conventional systems. The OCFS technology acts more like a biochemical system than living cells, so conditions can be exploited to make proteins of interest.
“It’s ‘open’ in the sense that different reagents can be added in a combinatorial fashion to find the right conditions for optimal protein synthesis,” says William J. Newell, CEO.
James Swartz, Sc.D., created the OCFS technology at Stanford University. Swartz removed the ribosomal machinery needed for protein transcription and translation from Escherichia coli and then transformed the key components into a cost-effective platform for protein manufacturing. The ribosomal machinery is contained in a cell-free extract that can be modified to carry out reactions under conditions that living cells cannot tolerate.
Swartz helped start Sutro Biopharma in 2003, based on the intellectual property that he developed surrounding the E. coli cell extract and its modifications. The cell-free expression system can produce peptides, cytokines, antibodies, and other proteins in either small laboratory batches or larger quantities.
“The cell-free extract is the same regardless of the peptide or protein that will be synthesized. That’s a fundamental difference that distinguishes our method from other cellular expression systems,” says Newell.
Among the challenges Swartz faced was how to fuel large-scale protein production. For small laboratory research, ATP fuels the ribosomal machinery, but the amount of ATP required for large-scale protein synthesis is cost prohibitive.
Swartz solved the problem by using cheaper energy sources to activate oxidative phosphorylation pathways, which, in turn, generate ATP for the ribosomal machinery. “This is a fundamental part of the IP that we licensed exclusively from Stanford,” says Newell.