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

Abstract

Virus-like particles (VLPs) derived from Leviviridae virions contain substantial amounts of cellular and plasmid-derived RNA. This encapsidated polynucleotide serves as areservoir 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 as ignificant entropic cost for the reptation of long chains through the capsid pores.C argo molecules were released over periods of 20-120 hours following simple reversible first-order kinetics in most cases.T hese observations define as imple general method for the noncovalent packaging,a nd subsequent release,o ff unctional molecules inside nucleoprotein nanocages in am anner independent of modifications to the capsid protein.

Modular Catalysis: Aptamer Enhancement of Enzyme Kinetics in a Nanoparticle Reactor

“…Diffusion of the small-molecule substrate and products through the capsid protein is assumed to be essentially unconstrained, as we have shown in a different context. 72 Because the effect of packaged aptamer is sequencedependent, relying on sequences having specific affinity for the cocaine substrate, the aptamer can only improve enzyme performance if it increases the local substrate concentration but releases the substrate easily enough to be processed by the enzyme. Thus, the binding constant added to the system by the presence of the aptamer (K A-S ) can neither be too large (insufficiently able to capture enough substrate in the particle to make a difference) nor too small (unable to release enough substrate in the vicinity of the enzyme).…”

“…A model of the relevant interactions in this system is shown in Figure . Diffusion of the small-molecule substrate and products through the capsid protein is assumed to be essentially unconstrained, as we have shown in a different context . Because the effect of packaged aptamer is sequence-dependent, relying on sequences having specific affinity for the cocaine substrate, the aptamer can only improve enzyme performance if it increases the local substrate concentration but releases the substrate easily enough to be processed by the enzyme.…”

Sequential Two-Photon Delayed Fluorescence Anisotropy for Macromolecular Size Determination

“…For better control of particle size and more biological relevance, we used OADFA to determine the size of Qβ, a recombinant virus-like particle (VLP) derived from an E. coli bacteriophage (Leviviridae) . , This self-assembled macromolecular assembly forms a highly stable container − that can be used for cargo delivery, , and VLPs were loaded with the fluorescent protein mVenusa fluorescent protein we have shown to exhibit OADF. ,, Qβ-mVenus OADFA yields a measured radius of 12.5 ± 0.6 nm, which is very close to the radius measured by dynamic light scattering (DLS) (Figure C) and TEM (Figure S3).…”

Exosomes-based particles as inhalable COVID-19 vaccines

“…Besides, several vaccines need to be stored in deep freezing condition to keep efficacy of bioactive, which has brought great cost and difficulties in long-term storage and transportation. Virus-like particles (VLPs), usually an artificial nanostructure, own similar morphology to natural virus yet fail to reproduce the virus and infect host [ [17] , [18] , [19] ], which could trigger robust cellular or humoral immunity reaction to against virus invasion [ 20 , 21 ]. Particularly, exosomes are a class of naturally-derived extracellular vesicles (approximately 100 ​nm in diameter) secreted from most cells, which have raised remarkable attention in drug delivery and immunization area [ 16 ] ( Fig.…”