Artificial viral shells for pinpoint drug delivery

Researchers at the Technion-Israel Institute of Technology and The Scripps Research Institute in California are designing an artificial viral shell as a valuable nano-container for pinpoint drug delivery, molecular computing components, and a host of other applications.

Technion chemist Ehud Keinan and colleagues were inspired by the construction of natural viral capsids, which enclose a virus's genetic material within a sphere knitted together from identical protein building blocks.

Like a soccer ball – or its nano-equivalent the carbon buckyball – the viral capsid combines these protein units into a sphere with a large surface to volume ratio—that is, a tiny sphere with a relatively roomy interior. These design features, combined with the fact that viral capsids assemble themselves with little prompting, make the capsid an excellent model for artificial nano-capsules, the researchers report in the Proceedings of National Academy of Sciences this week.

Artificial capsids could act as cargo containers that deliver drugs to targeted areas of the body, vessels that shuttle replacement genes to their new homes in the genome as part of gene therapy, or tiny enclosed laboratories for doing chemical reactions or building molecular computer parts.

Keinan said the size of artificial capsids “is very important. It will determine which molecules we'll be able to pack inside the container. Small containers will allow for drug delivery, big ones for delivering proteins and very big for the delivery of genes.”

The researchers decided to pick apart the construction of viral capsids to determine exactly how their identical parts come together. They built a handful of pentagonal tiles with magnetic edges that mimic the chemically-bonding edges of natural capsid proteins. In some of their first experiments, they simply shook the magnetic tiles together in a plastic jar and watched the pieces snap together to form a sphere.

“Although intellectually we knew that this type of self-organization occurs spontaneously, watching it happen from random shaking on the macroscopic scale was inspirational,” Keinan and colleagues write in their paper.

The researchers then turned to computer simulations of capsid construction, working with the dish-shaped chemical compound called corannulene. Also called the buckybowl, corannulene has a five-sided symmetry and rigid curve that makes it a potentially good building block for an artificial capsid.

In the simulations, Keinan and colleagues experimented with different chemical “sticky edges” to the corannulene building blocks to determine the conditions under which the corannulene units would self-assemble into a ball. They created a half-sphere in the simulation, and expect to have a full sphere soon.

By applying different kinds of chemical bonds at the sticky edges—from weak hydrogen bonds to metal bonds to strong disulfide bonds—the researchers believe they can alter the strength of the capsid and affect the conditions under which it assembles or disassembles, Keinan said.

Although the researchers have yet to build an artificial capsid in the lab, “the present study gives us confidence that we can design molecules based on these principles that can assemble into chemical capsids,” they write.

The Technion-Israel Institute of Technology is Israel's leading science and technology university. Home to the country's winners of the Nobel Prize in science, it commands a worldwide reputation for its pioneering work in nanotechnology, computer science, biotechnology, water-resource management, materials engineering, aerospace and medicine. The majority of the founders and managers of Israel's high-tech companies are alumni. Based in New York City, the American Technion Society (ATS) is the leading American organization supporting higher education in Israel, with 21 offices around the country.