Noble, J E; Hsiao, Y-W; Kepiro, I E; de Santis, E; Hoose, A; Augagneur, C; Lamarre, B; Briones, A; Hammond, K; Bray, D J; Crain, J; Ryadnov, M G (2024) A non-linear peptide topology for synthetic virions. ACS Nano, 18 (43). pp. 29956-29967.

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Abstract

a non-linear de novo peptide topology for the assembly of synthetic virions is reported. The topology is a backbone cyclized amino-acid sequence in which polar L- and hydrophobic D-amino acid residues of the same-type alternate. This arrangement introduces pseudo C4 symmetries of side chains within the same cyclopeptide ring, allowing for the lateral propagation of cyclopeptides into networks with a [3/6, 4]-fold rotational symmetry closing into virus-like shells. A combination of computational and experimental approaches was used to establish that the topology forms morphologically uniform, non-aggregating and non-toxic nanoscale shells. These effectively encapsulate genetic cargo and promote its intracellular delivery and a target genetic response. The design introduces a nanotechnology inspired solution for engineering virus-like systems thereby expanding traditional molecular biology approaches used to create artificial biology to chemical space.

Item Type:	Article
Keywords:	gene delivery, cyclopeptides, engineering biology, protein design, synthetic viruses, nanoscale imaging
Subjects:	Biotechnology > Biopharmaceutical Manufacturing and Characterisation
Divisions:	Chemical & Biological Sciences
Identification number/DOI:	10.1021/acsnano.4c10662
Last Modified:	23 May 2025 14:20
URI:	https://eprintspublications.npl.co.uk/id/eprint/10171