Protein and Nucleic Acid Delivery Vehicles, Components and Mechanisms Thereof

摘要

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.

主权项

1. A method comprising the following steps:
(a) attaching a packaging motor to a carrier, and (b) transferring an exogenous material into an inner compartment of the carrier to thereby form a packaging machine, wherein the carrier is a bacteriophage component, wherein the bacteriophage component is encoded by a nucleic acid comprising a mutation in a bacteriophage neck and/or tail protein, wherein the packaging motor comprises a protein complex, and wherein the protein complex comprises one or more subunits of gene product (gp) 17 protein.