Dr. Jeffrey Way started off session 2 on biomedical
applications at the SEED (Synthetic Biology: Engineering, Evolution and Design)
conference by talking about the application of synthetic biology in protein
drug design and production. Protein
drugs are essentially drugs that either target proteins thereby blocking their
activity or replace a missing protein (as in case of diabetes or anemia).
Dr. Way discussed how nature uses highly complex systems to
achieve immune responses – multiple proteins interact with multiple ligands and
this complex network is constantly edited by evolution.
At its core, Synthetic Biology is about learning from Nature
and improving our methods of producing organic compounds. Borrowing a leaf from
redundant and complex mammalian pathways Dr. Way proposed to improve
specificity of protein drugs in two ways – first, by introducing minor
mutations in the proteins such that their affinity to bind to non-targets
reduces, albeit at the cost of 40x-200x reduction in target-specific activity and
second, by physically linking the protein to another protein that will bind to a
spatially nearby cell-surface receptor.
Dr. Way and others in the Dr. Pamela Silver lab have
demonstrated the aforementioned strategies using two protein drug systems – the
IFNα
and Erythropoietin (EPO). This technology holds promise in the billion-dollar
field of EPO production – the key drug for anemia - but work needs to be done
in making this suitable for scenarios such as “solid” tumors that are rendered
inaccessible due to lack of proper exchange of fluids with lymph nodes and are
impervious to diffusion.
To address the current challenges in protein drug design, Dr. Way
urged the need for computational tools that would allow spatial optimization of
protein-protein complexes and increase the throughput of the current method of experimental
trial and error.
For more information, visit their lab site: https://silver.med.harvard.edu/
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