Abstract: Described is T4 DNA packaging machine comprising: one or more DNA molecules packaged in a head of the T4 DNA packaging machine, one or more Hoc-fused proteins displayed on the head of the T4 DNA packaging machine, and one or more Soc-fused proteins displayed on the head of the T4 DNA packaging machine. Also described are methods of making and using such a T4 DNA packaging machine.

Abstract: Complex viruses are assembled from simple protein subunits by sequential and irreversible assembly. During genome packaging in bacteriophages, a powerful molecular motor assembles at the special portal vertex of an empty prohead to initiate packaging. An aspect of the invention relates to the phage T4 packaging machine being highly promiscuous, translocating DNA into finished phage heads as well as into proheads. Single motors can force exogenous DNA into phage heads at the same rate as into proheads and phage heads undergo repeated initiations, packaging multiple DNA molecules into the same head. This shows that the phage DNA packaging machine has unusual conformational plasticity, powering DNA into an apparently passive capsid receptacle, including the highly stable virus shell, until it is full. These features allow for the design of a novel class of nanocapsid delivery vehicles.

Abstract: Described herein is a soluble HIV-1 retrovirus transmembrane glycoprotein gp41 trimer (Soc-gp41M-Fd) containing a partial ectodomain and the cytoplasmic domain, that is fused to the small outer capsid (Soc) protein of bacteriophage T4 and the Foldon domain of the bacteriophage T4 fibritin (Fd). The gp41 trimer that has a prehairpin structure could be utilized to understand the mechanism of viral entry and as a candidate for development of HIV-1 vaccines, diagnostics and therapeutics. Other secondary embodiments of the gp41 proteins containing different modifications are also disclosed. According to one embodiment, the gp41 trimer is further attached to a cell penetration peptide (CPP). Methods of producing gp41 trimers are also disclosed.

Abstract: Complex viruses are assembled from simple protein subunits by sequential and irreversible assembly. During genome packaging in bacteriophages, a powerful molecular motor assembles at the special portal vertex of an empty prohead to initiate packaging. An aspect of the invention relates to the phage T4 packaging machine being highly promiscuous, translocating DNA into finished phage heads as well as into proheads. Single motors can force exogenous DNA into phage heads at the same rate as into proheads and phage heads undergo repeated initiations, packaging multiple DNA molecules into the same head. This shows that the phage DNA packaging machine has unusual conformational plasticity, powering DNA into an apparently passive capsid receptacle, including the highly stable virus shell, until it is full. These features allow for the design of a novel class of nanocapsid delivery vehicles.