Transport of Molecular Cargo by Interaction with Virus‐Like Particle RNA

Abstract

AbstractVirus‐like particles (VLPs) derived from Leviviridae virions contain substantial amounts of cellular and plasmid‐derived RNA. This encapsidated polynucleotide serves as a reservoir for the efficient binding of the intercalating dye thiazole orange (TO). Polyethylene glycol (PEG) molecules and oligopeptides of varying length, end‐functionalized with TO, were loaded into VLPs up to approximately 50 % of the mass of the capsid protein (hundreds to thousands of cargo molecules per particle, depending on size). The kinetics of TO–PEG binding included a significant entropic cost for the reptation of long chains through the capsid pores. Cargo molecules were released over periods of 20–120 hours following simple reversible first‐order kinetics in most cases. These observations define a simple general method for the noncovalent packaging, and subsequent release, of functional molecules inside nucleoprotein nanocages in a manner independent of modifications to the capsid protein.