Artificial Viruses: Exploiting Viral Trafficking for Therapeutics

Abstract

Improved understanding of the signals that direct the intracellular transport of endogenous mammalian proteins, as well as the means by which viral invaders hijack transport pathways during infection, has revealed a plethora of methods for enhancing drug and gene delivery. Multi-component delivery vectors with virus-like functionality are being developed to assemble with therapeutic DNA into structured nanoparticles that are internalized and actively transported to specific locations within mammalian cells. Furthermore, the mimicking of viral mechanisms can be extended to nuclear maintenance and replication of exogenous DNA, through either site-specific integration into safe genomic regions, or extra- chromosomal maintenance as episomally replicating plasmids. The development of increasingly sophisticated artificial viruses has enormous potential to overcome numerous intracellular barriers that have, thus far, prevented efficient and sustained non-viral gene therapy.

Self-Amplifying mRNA Vaccines

“…Viruses have evolved sophisticated mechanisms that exploit or circumvent cellular signaling and transport pathways to traffic within host cells and deliver their genome into the appropriate subcellular compartment (Glover, 2012). Therefore, it is worth reviewing viral delivery of selfamplifying mRNA.…”

Protein Calligraphy: A New Concept Begins To Take Shape

“… 51 These multicomponent delivery vectors have virus-like functionality, and mimic the ability of viruses to target and enter specific cells, with the release of their drug/DNA cargo triggered by a decrease in the pH of the endosome/lysozyme. 52 The assembly of multiple cages ( Figure 4 A) would also facilitate the creation of structures with high porosity. 16 Highly porous materials, as exemplified by metal–organic frameworks (MOFs), 53 have been examined for applications in catalysis, gas storage, and biomimetic mineralization; 54 presumably protein nanostructures could find similar roles, especially as scaffolds for three-dimensional tissue culture.…”

“…Indeed, functionalization of protein delivery vectors with subcellular targeting signals can facilitate the active transport and delivery of therapeutic drugs to specific locations within mammalian cells . These multicomponent delivery vectors have virus-like functionality, and mimic the ability of viruses to target and enter specific cells, with the release of their drug/DNA cargo triggered by a decrease in the pH of the endosome/lysozyme . The assembly of multiple cages (Figure A) would also facilitate the creation of structures with high porosity .…”

Modular Nanotransporters for Nuclear-Targeted Delivery of Auger Electron Emitters

“…This review focuses on MNT delivery of AEEs; delivery of photosensitizers and other molecules by MNTs has been reviewed earlier (Sharman et al, 2004; Glover, 2012; Simoes et al, 2015; Slastnikova et al, 2015; Ulasov et al, 2018). …”