Objective 8

Development of protein nanocontainers and nanocarriers


Viral capsids are closed compartments built of multiple copies of one or a few proteins. Due to their stability and versatility, capsids can be used as vehicles for the encapsulation of materials for nanotechnological appplications. In appropriate conditions, capsid structural units self-assemble into virus-like particles (VLP), macromolecular assemblies structurally identical to virions that are generated by recombinant expression of one or more capsid proteins. VLP are excellent models for container engineering, since structural units can be modified to alter capsid size. In addition, chemical and genetic modifications of capsid proteins and nucleic acids allow alteration of VLP properties for use as nanotransporters, as platforms for specific positioning of compounds on the inner and/or outer capsid surfaces.


Fig.1 Three-dimensional maps of icosahedral viruses, VLPs and helical assemblies from two-dimensional cryo-electron microscopy images. IBDV, infectious bursal disease virus (T=13l capsid, left; T=7 capsid (blue), right); HvV190s, Helminthosporium victoriae 190S virus; PcV, Penicillium chrysogenum virus; HRV2, human rhinovirus A2; CCMV, cowpea chlorotic mottle virus (T=3 capsid, left; T=1 capsid, right); RHDV, rabbit hemorrhagic disease virus; SVP T=1, IBDV subviral T=1 particles; T/, T7 bacteriophage head (left) and prohead (right); pVP2, helical assembly of IBDV pVP2.



Fig.2. Assembly of virus-like particles (VLPs) can be used for precise positioning of functional species, at inner and/or outer surfaces, or as nanocontainers to encapsulate different types of materials. These modified protein cages offer great opportunities in nanotechonology and nanomedicine. We have used for this purpose the cowpea chlorotic mottle virus (CCMV) and an organic dye as phatalocyanine (ZnPc). (A) Self-assembly of 10 nm ZnPc nanospheres within a 20 nm (T=1) protein cage formed by CCMV capsid protein (CP) dimers. (B) Encapsulation of ZnPc dimers in 28 nm T = 3 CCMV capsids (Chem. Science 5: 575-581, 2014).