Scientists at the University of Washington Institute of Protein Design have designed and produced a self-assembling protein shell shaped like an icosahedron, similar to those that encapsulate viruses. The researchers believe their work may open new paths for engineering cargo-containing nanocages to package and deliver drugs and vaccines directly into cells or building small reactors to catalyze biochemical reactions.
The protein designers took their cue from the many viruses that transport their genomes inside protective icosahedral protein shells, i.e., viral capsids. The researchers' paper (“Design of a Hyperstable 60-Subunit Protein Icosahedron”), published in Nature, reports on their computational design and experimental testing of a highly stable icosahedral protein nanocage.
Engineered at the atomic level, this nanocage can construct itself from biochemical building blocks and information encoded in strands of DNA. After selecting the design for this icosahedral nanocage through computer modeling, the researchers produced it in bacteria. Electron microscopy of the resulting icosahedral particles confirmed that they were nearly identical to the design model.
The leads on the project were Yang Hsia, a University of Washington graduate student in biological physics, structure, and design, and Jacob B. Bale, Ph.D., a recent graduate from the UW molecular and cellular biology doctoral program and now a research scientist at Arzeda in Seattle.
The senior authors were Neil P. King, Ph.D., translational investigator at the UW Institute for Protein Design, and David Baker, Ph.D., director of the Institute and UW professor of biochemistry. Dr. Baker is also an investigator with the Howard Hughes Medical Institute.
“The ability to design proteins that self-assemble into precisely specified, robust, and highly ordered icosahedral structures,” the researchers wrote, “would open the door to a new generation of protein containers with properties custom-made for applications of interest.”
Among these applications might be fabricating nanoscale icosahedral vehicles. Such research might create tiny, spacecraft-like devices that could encapsulate and deliver therapies directly to specific types of cells, such as cancer cells.
The designed icosahedron, while sturdy, proved to disassemble and reassemble itself under certain environmental conditions. This reversible property is essential if it eventually becomes part of packaging, carrying and delivering a biochemical payload.
In addition, the flexibility to modify these miniature cages, according to the investigators, “should have considerable utility for targeted drug delivery, vaccine design and synthetic biology.”
The newly designed icosahedron has a considerably larger internal volume than previously designed nanocages of other shapes and so could hold more cargo as molecular shipping containers.