A De Novo Virus-Like Topology for Synthetic Virions

Abstract

A de novo topology of virus-like assembly is reported. The design is a trifaceted coiled-coil peptide helix, which self-assembles into ultrasmall, monodisperse, anionic virus-like shells that encapsulate and transfer both RNA and DNA into human cells. Unlike existing artificial systems, these shells share the same physical characteristics of viruses being anionic, nonaggregating, abundant, hollow, and uniform in size, while effectively mediating gene silencing and transgene expression. These are the smallest virus-like structures reported to date, both synthetic and native, with the ability to adapt and transfer small and large nucleic acids. The design thus offers a promising solution for engineering bespoke artificial viruses with desired functions.

Peptide Nanomaterials Designed from Natural Supramolecular Systems

“…De novo design of coiled‐coil peptides is a useful methodology to construct self‐assembled AVCs because of our deep understanding of the principles for specific interaction pairs . For instance, Ryadnov et al.…”

“…For instance, Ryadnov et al. developed dendrimeric virus‐like assembly based on a self‐complementary coiled‐coil subunit having three interfacial facets (Figure b) . The coiled‐coil dimer with a disulfide bond self‐assembled to form 12‐nm monodisperse spherical shells.…”

“…De novo design of coiled-coil peptides is a useful methodology to construct self-assembled AVCs because of our deep understanding of the principles for specific interaction pairs. [67][68][69][70][71] For instance, Ryadnov et al developed dendrimeric virus-like assembly based on a self-complementary coiledcoil subunit having three interfacial facets (Figure 6b). [71] The coiled-coil dimer with a disulfide bond self-assembled to form 12-nm monodisperse spherical shells.…”

Rationally Designed Peptidyl Virus‐Like Particles Enable Targeted Delivery of Genetic Cargo

“…[4] Forexample,Niand Chau reported the synergistic co-assembly of peptide and plasmid DNAi nto stable virus-like nanococoons with high gene-transfection efficacy. [6] These pioneering works offer promising strategies for the design of virus alternatives. [6] These pioneering works offer promising strategies for the design of virus alternatives.…”

“…[6] These pioneering works offer promising strategies for the design of virus alternatives. [4b-e, [5][6]8] Rational design of at argeting pVLP co-assembled from peptides derived from the original virus thus remains ag reat challenge. [4b-e, [5][6]8] Rational design of at argeting pVLP co-assembled from peptides derived from the original virus thus remains ag reat challenge.…”