Nanoparticulate Architecture of Protein-Based Artificial Viruses Is Supported by Protein–DNA Interactions

Abstract

The structural analysis of the protein in these hybrid nanoparticles indicates a molecular conformation with predominance of α-helix and the absence of cross-molecular, β-sheet-supported protein interactions. The nanoscale organizing forces generated by DNA-protein interactions can then be observed as a potentially tunable, critical factor in the design of protein-only based artificial viruses for gene therapy.

Molecular biology of oncogenic inflammatory processes. I. Non-oncogenic and oncogenic pathogens, intrinsic inflammatory reactions without pathogens, and microRNA/DNA interactions (Review)

“…The haploid germ cells in their unisons become differentiating somatic cells. However, the selfrenewing stem cells, instead of the route to differentiation, may choose a reversal toward a primordial stage of life: restoring the ancient DNA and the ways it existed under precellular conditions intimately reacting with RNA and with 'amorphous proteins', as amino acid chains 'selfreplicating' (603,604). In the first cellular life forms, DNA was highly resistant to physicochemical damage and voraciously accepting for fusion and recombination alien genomic sequences (62).…”

“…In the first cellular life forms, DNA was highly resistant to physicochemical damage and voraciously accepting for fusion and recombination alien genomic sequences (62). Upon the encounter of amorphous proteins and naked DNA, the proteins engulf the DNA and DNA strands penetrate to the helices of the proteins, while the proteins undergo subtle morphological changes of their nanoparticulate architecture (604). Innumerable such newly formed structures may exist in nature without being able to enter cells for replications, inasmuch as the natural proteins can not serve as specific ligands to any cell receptors (whereas, the proteins generated in the DomingoEspin laboratory were actually encoded by borrowed viral genes from the foot and mouth virus and from the SV40 virus, and thus have become 'artificial viruses' able to react with cell and nuclear membrane receptors and transgress them) (604).…”

“…Upon the encounter of amorphous proteins and naked DNA, the proteins engulf the DNA and DNA strands penetrate to the helices of the proteins, while the proteins undergo subtle morphological changes of their nanoparticulate architecture (604). Innumerable such newly formed structures may exist in nature without being able to enter cells for replications, inasmuch as the natural proteins can not serve as specific ligands to any cell receptors (whereas, the proteins generated in the DomingoEspin laboratory were actually encoded by borrowed viral genes from the foot and mouth virus and from the SV40 virus, and thus have become 'artificial viruses' able to react with cell and nuclear membrane receptors and transgress them) (604). In contrast, the natutally formed entities may show up in the metagenomic samples (in a mixture with regular incomplete virions), as the 'gene transfer agents' of Kristensen et al (605), or among the structures considered to form a 'fourth domain of life' on Earth (606).…”

“…That world can not only be imagined, but could possibly be duplicated in the laboratory. How the naked DNAs interacted with amorphous amino acid clusters (603,604), hypercycling RNAs in the hydrothermal vents at the bottom of the oceans (and in their laboratory reactors) (630), the catalytic hammerhead ribozymes (631), and the circular selfreplicating ('rolling circle') viroid RNAs (preserved from the precellular world in extant plant and mammalian cells, the hepatitis δ viroid, some with a tandemly repeated homologous DNA attached) (632635)? In order to envision these interactions in a most hostile precellular environment without potent protein enzymes, that were not being able to form without cellular ribosomes and without a genetic code, both advanced knowledge in proteomics and genomics, and a great deal of imagination, are required.…”

Modular Multifunctional Protein Vectors for Gene Therapy

“…For instance, in the absence of DNA, the HNRK modular vector that uses poly-lysine for DNA condensation, self-organize as amorphous, polydisperse particulate entities ranging from a few nanometres up to around one micron. However, in the presence of DNA, protein-DNA complexes appear as tight and rather monodisperse spherical-like nanoparticles of around 80 nm in diameter (Domingo-Espín et al 2011). The most widely used condensing agent is a poly-lysine chain (Saccardo et al 2009).…”