4.8 Article

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

Journal

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 2, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202111687

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Funding

  1. Defense Threat Reduction Agency [HDTRA11810029]
  2. National Institutes of Health [1R01 AI139748]
  3. U.S. Department of Defense (DOD) [HDTRA11810029] Funding Source: U.S. Department of Defense (DOD)

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This study identified a simple general method for non-covalent packaging and subsequent release of functional molecules inside nucleoprotein nanocages, independent of modifications to the capsid protein.
Virus-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 non-covalent packaging, and subsequent release, of functional molecules inside nucleoprotein nanocages in a manner independent of modifications to the capsid protein.

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