Encapsulation of mrna into artificial viral capsids via hybridization of a β-annulus-dt20 conjugate and the poly(A) tail of mrna

Abstract

Messenger RNA (mRNA) drugs have attracted considerable attention as promising tools with many therapeutic applications. The efficient delivery of mRNA drugs using non-viral materials is currently being explored. We demonstrate a novel concept where mCherry mRNA bearing a poly(A) tail is encapsulated into capsids co-assembled from viral β-annulus peptides bearing a 20-mer oligothymine (dT20) at the N-terminus and unmodified peptides via hybridization of dT20 and poly(A). Dynamic light scattering measurements and transmission electron microscopy images of the mRNA-encapsulated capsids show the formation of spherical assemblies of approximately 50 nm. The encapsulated mRNA shows remarkable ribonuclease resistance. Further, modification by a cell-penetrating peptide (His16) on the capsid enables the intracellular expression of mCherry of encapsulated mRNA.