Virus-like particles (VLPs) have attracted great interest in pharmaceutical and biotechnological research.[1] VLPs are typically composed of recombinant proteins, for example, the capsid of the hepatitis B virus,[2] sometimes in combination with nucleic acids, such as bacteriophage,[3] or they may contain a viral envelope in addition to viral coat proteins, such as virosomes.[4] The natural self-assembling core structures of many natural VLPs can be exploited to display multiple copies of an antigen across the surface of the particle, for example, by inserting oligonucleotides encoding peptide loops into the appropriate structural genes, or by chemically conjugating haptens to recombinant VLPs. The importance of displaying repeated antigenic structures across a viral or bacterial surface to generate robust immune responses is now well established.[5, 6] VLPs may also contain natural T-helpercell epitopes and pathogen-associated molecular patterns that are recognized by the innate immune system, which further enhance immune responses. All the previously described VLPs, however, require the use of cell-culture or recombinant-DNA methods for production and/or engineering. We have explored the possibility of producing VLPs using artificial synthetically derived building blocks, which can self-assemble into particles having a size and composition similar to that of natural viruses, in this case containing protein and lipid, but not nucleic acids. Such synthetic viruslike particles (SVLPs) might then retain the advantages of naturally derived VLPs as antigen delivery vehicles, but in addition could be optimized and produced using a myriad of synthetic chemical methods.

The SVLPs described herein harness the principles of protein–protein as well as lipid–lipid recognition to drive selfassembly. The basic building block comprises a lipopeptide containing a coiled-coil sequence.[7] The coiled-coil motif drives self-assembly of the peptide chains into parallel helical bundles. In addition, a lipid component, typically a phospholipid having two long fatty acid chains, is coupled at the N terminus of each peptide chain. After self-association of the coiled coil into a parallel helical bundle, the resulting cluster of lipid chains drives self assembly of multiple coiled-coil