Assembly and Stability of Virus Like Particles from the Gag Capsid Domain from the Human Endogenous Retrovirus HML‐2

Abstract The capsid domain of the Gag protein from the human endogenous retrovirus HML‐2 can form virus‐like particles (VLPs) in vitro . Such particles made from proteins from other organisms are used as nanocarriers. Repeated use of exogeneous VLPs may however lead to an immune response. Recombinantly produced and purified capsid domain from HML‐2 could, given its human origin, provide a nanocarrier system, which potentially could evade an immune response. It is however not known if capsids formed in vitro by the HML‐2 Gag capsid domain can be loaded with a molecular cargo and if such particles are stable. In this work, we investigated how the assembly efficiency change with conditions. We demonstrate that once formed the capsids are stable over a much broader range of pH than the range of pH that allows capsid formation, and that the capsids are stable for weeks. We furthermore show that HML‐2 capsids can encapsulate small molecules. Our results suggest that the HML‐2 capsids potentially may serve as stable nanocarriers protecting its cargo from the surrounding environment.