Tekewe, Alemu

Connors, Natalie K

Middelberg, Anton P J

Lua, Linda H L

2016

<p><b>Virus-like particles (VLPs) and capsomere subunits have shown promising potential as safe and effective vaccine candidates. They can serve as platforms for the display of foreign epitopes on their surfaces in a modular architecture. Depending on the physicochemical properties of the antigenic modules, modularization may affect the expression, solubility and stability of capsomeres, and VLP assembly. In this study, three module designs of a rotavirus hydrophobic peptide (RV10) were synthesized using synthetic biology. Among the three synthetic modules, modularization of the murine polyomavirus VP1 with a single copy of RV10 flanked by long linkers and charged residues resulted in the expression of stable modular capsomeres. Further employing the approach of module titration of RV10 modules on each capsomere via <i>Escherichia coli</i> co-expression of unmodified VP1 and modular VP1-RV10 successfully translated purified modular capomeres into modular VLPs when assembled <i>in vitro</i>. Our results demonstrate that tailoring the physicochemical properties of modules to enhance modular capsomeres stability is achievable through synthetic biology designs. Combined with module titration strategy to avoid steric hindrance to intercapsomere interactions, this allows bioprocessing of bacterially produced in vitro assembled modular VLPs.</b></p>

Protein Science, 25(8), p. 1507-1516

1469-896X

0961-8368

https://hdl.handle.net/1959.11/58569

en

Wiley-Blackwell Publishing, Inc

Design strategies to address the effect of hydrophobic epitope on stability and in vitro assembly of modular virus-like particle

Journal Article

Publication