Targeted delivery of RNA using synthetic bacterial spores

RNA therapy, which includes delivery of mRNA or siRNA, shows promise for treating various diseases, but difficulties in targeting specific cell types and low efficiency of loading RNA into nanoparticles remain hurdles to achieving widespread use. Previously, we reported the assembly of biocompatible synthetic bacterial spore-like particles, termed "SSHELs", which are built atop a porous silica core encased in a lipid bilayer and two bacterial proteins that form a stable proteinaceous surface that may be covalently modified with targeting proteins of interest. Here, we employ micron-scale SSHELs constructed using a fusogenic lipid and decorated with affibodies targeting cell surface HER2 to specifically deliver model mRNA and siRNA molecules specifically to HER2-positive ovarian and breast cancer cells, with high RNA loading efficiency and cargo capacity. SSHEL particles therefore represent a versatile vehicle for the delivery of not only small molecules, but also therapeutic RNA to specific cell types.