Cell-free Protein Engineering Research
The Bundy Biotechnology Research Lab engineers novel low-cost biosensors, next generation cancer therapeutics, on-demand magistral medicine production, optimized industrial biocatalysts, and vaccine production.
Cell-free Synthetic Biology for Protein Engineering
What is Cell-free Synthetic Biology?
Proteins—polymers of amino acids—are a major class of biomolecules whose myriad functions facilitate many crucial biological processes. Accordingly, human control over these biological processes depends upon the ability to study, produce, and modify proteins. One innovative tool for accomplishing these aims is cell-free protein synthesis (CFPS). This method, rather than using living cells to make protein, simply extracts the cells’ natural protein-making machinery and then uses it to produce protein in vitro.
Engineering Within a Cell-free System
Because living cells are no longer involved, scientists can freely adapt and engineer the protein production environment in ways not otherwise possible. This increased accessibility enables cutting-edge research on current topics such as unnatural amino acid insertion, virus-like particle production, enzyme immobilization, and high-throughput assays.
These exciting areas of study enable new biosensor designs, biotherapeutics, cancer treatments, vaccine development, and biocatalysis stabilization.
Extreme-low Cost Cancer Therapeutics Magistrally Produced
We have developed endotoxin, freeze-dried cell-free reagents capable of shelf-stability for months to years through cryoprotectants. We have also demonstrated the production of an FDA-approved protein therapeutic for Acute Lymphoblastic Leukemia (the most common form of childhood cancer) in a few hours at the point of care to address maufacturing problems that commonly lead to world wide shortages of this drug.
The engineering of virus-like particles for highly specific imaging agents, drug delivery vehicles, and vaccine antigens is another major thrust of the Bundy Lab. Separately, the engineering of more effective cancer Therapeutics has been initiated as a new research project.
Icosahedral virus like particle (VLP) is a hollow spherical protein container. Hundreds of identical monomer self-assemble to become a microcompartment. VLPs are genetically modifiable. This property enables us to purify them, encapsidate guest molecules, or decorate the exterior surface with ligands, dye, etc. Currently many biotechnologists utilize VLPs to make drug delivering vehicles, bioimaging materials, vaccines, biochemical reaction vessels.
Next Generation Protein/Cancer Therapeutics
In collaboration with the Knotts Lab at BYU, we have combined course grain simulation with high-throughput cell-free expression to optimize the PEGylation location on proteins for retained function and activity. Most 2nd generation protein therapeutics are simply the PEGylated version of the 1st generation drug to improve pharmacokinetics and stability. However, this is currently not optimized for each protein and greater than 90% of the original activity can be lost upon PEGylation. This work could enable lower costs, few doses, and fewer side effects for 2nd generation therapeutics.
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Dr. Bundy’s research team would like to thank the following for providing funding for our research.
DARPA (Department of Defense)
National Science Foundation (CBET Division)
National Pork Board (Foreign Animal Disease)
NASA (Rocky Mountain Space Grant Consortium)
BYU (ORCA/Graduate Studies)