“Encapsulation of Semiconducting Polymers in Vault Protein Cages”
A Semiconducting polymer [poly(2-methoxy-5-propyloxy sulfonate phenylene vinylene), MPS-PPV] can be encapsulated inside recombinant, self-assembling protein nanocapsules called “vaults”.
Polymer incorporation into these nanosized protein cages, found naturally at -10,000 Copies Per Human Cell, was confirmed by fluorescence spectroscopy and small-angle X-ray scattering.
Although vault cellular functions and gating mechanisms remain unknown, their large internal volume and natural prevalence within the body suggest they could be used as carriers for therapeutics & imaging reagents.
This study provides the groundwork for the use of vaults in encapsulation and delivery applications.
“Targeting Vault Nanoparticles to Specific Cell Surface Receptors”
As a naturally occurring nanocapsule abundantly expressed in nearly all eukaryotic cells, the barrel-shaped vault particle is an ideal structure to engineer for targeting to specific cell types.
Recombinant vault particles self-assemble from 96 copies of the major vault protein (MVP), have dimensions of 72.5 X 41 nm and have a hollow interior large enough to encapsulate hundreds of proteins.
Three different tags were engineered onto the C-terminus of MVP:
An 11 amino acid epitope tag, a 33 amino acid lgG-binding peptide, and the 55 amino acid Epidermal growth factor (EGF).
These modified vaults were produced using a baculovirus expression system.
This demonstrate that recombinant vaults assembled from MVP’s containing C-terminal peptide extensions display these tags at the top and bottom of the vault of the outside of the particle and can be used to specifically bind the modified vaults to epithelial cancer cells (A431) via the epidermal growth factor receptor (EGFR) epithelial cancer cells (A431) via the epidermal growth factor receptor (RGFR) either directly (EGF modified vaults) or as mediated by a monoclonal antibody bound to recombinant vaults containing the peptide.
The ability to target vaults to specific cells represents an essential advance toward using recombinant vaults as delivery vehicles.
“Vault Nanoparticles Containing an Adenovirus-Derived Membrane Lytic Protein Facilitate Toxins and Gene Transfer”
Nonviral methods of gene delivery possess several advantages over that of viral-based vectors, including increased safety.
The goal is to transport molecules across host cell membranes with nonviral methods.
Cell-derived vaults are transfer vehicles for various foreign molecles.
Recombinant vault particles enter cells via macropinocytosis or phagocytosis but lack demonstrable membrane penetrating activity.
Internalization of vault-pVI complex into murine macrophages promoted co-delivery of a soluble ribotoxins or a cDNA plasmid encoding GFP.
Vault particles can be modified to enhance cell transfer of molecules.
This technology has the potential for delivering life-saving vaccines.
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