Nanoassembly of Oligopeptides and DNA Mimics the Sequential Disassembly of a Spherical Virus

• Published in: Angewandte Chemie International Edition Vol. 59; no. 9; pp. 3578 - 3584
• Main Authors: Ni, Rong, Chau, Ying
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 24-02-2020
• Edition: International ed. in English
• Subjects: Amino acids; artificial viruses; Capsid - chemistry; Deoxyribonucleic acid; Dismantling; DNA; DNA - chemistry; DNA structure; Gene expression; gene technology; Gene transfer; Genetic transformation; Genomes; HEK293 Cells; Humans; Hydrogen-Ion Concentration; Low aspect ratio; Microscopy, Fluorescence; Morphology; Nanostructures - chemistry; Nuclease; Oligopeptides; Oligopeptides - chemistry; Packaging; Particle Size; peptides; pH effects; spherical viruses; Virion - chemistry; Virus Assembly; Viruses; peptides; spherical viruses; artificial viruses; DNA; gene technology
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201913611

Protein subunits of a low aspect ratio (width over length) with stimuli‐responsiveness are hallmark building blocks of spherical viruses. The interaction of these repeating subunits enables hierarchical assembly for genome packaging and sequential disassembly for optimal genome release. Here, we mimicked these features and constructed a functional spherical artificial virus. The rationally designed 22‐amino acid peptide containing pH‐sensitive histidines and aromatic residues self‐assembled into homogenous nanodiscs of a low aspect ratio (≈7×7×4 nm). In the presence of DNA, the inter‐nanodisc interactions drove the formation of a viral capsid‐like structure enclosing DNA in the interior. This artificial virus roughly 50 nm in diameter underwent partial disassembly in response to acidic pH. The resulting intermediate with lowered DNA‐binding affinity continued to protect DNA from nuclease digestion. Such nanostructures, which mimic the intricate morphology and the intracellular transformation of spherical viruses, can be useful for constructing synthetic gene delivery vehicles, as evidenced by their efficient transgene expression.
En route to gene‐delivery vehicles: A peptide–DNA spherical artificial virus was formed by the hierarchical assembly of a peptide and DNA through inter‐subunit association. This nanostructure undergoes sequential disassembly at pH 5.