Genetic medicines, like those based on CRISPR/Cas9, need a delivery method to reach their intended destination. One popular vector to accomplish this is hollowed-out adeno-associated viruses. By repurposing a biological structure that’s evolved to enter cells, it’s possible to introduce genetic medicine instead of viral material. However, these viral vectors can’t hold a very big payload, being restricted to about 4.7 kilobases.
Some researchers believe it’s possible to design a better capsid without the need to rely on a viral vector. In two papers, researchers from the Institute for Protein Design, New York University (NYU) Langone Medical Center, and Pohang University of Science and Technology detail systems for developing both one-component and two-component “cages” (Nature 2026, DOI: 10.1038/s41586-026-10554-z and 10.1038/s41586-026-10464-0).
The cages are arranged in a hexagonal lattice structure that allows for a bigger sphere, but with pentagon “defects” interspersed. As soccer balls and buckminsterfullerene also demonstrate, the pentagons encourage curvature, which allows the lattice to close in a sphere-like shape. By tuning the curvature, the capsid designers could program the cage to assemble into spheres ranging from tens to hundreds of nanometers.
While the one-component cages are made of just one protein, the two-component system, which has been developed further than the one-component system, consists of homotrimers and linkers.
Beyond potentially delivering genetic medicines, Shunzhi Wang, one of the lead authors from NYU Langone, says the paper broadens what’s possible in the geometry of designed protein structures. “It opens up a new paradigm where you can design things that don’t strictly obey this icosahedral symmetry,” he says.
