Computational design of de novo protein nanoparticles for RNA delivery

Abstract

Several non-porous RNA encapsulating protein nanoparticles have been reported, but none have been shown to deliver nucleic acids to mammalian cells. Here, I will discuss my efforts to optimize the topology of a de novo pH-responsive trimer for docking into larger protein nanoparticles, and the design and screening of a library of such nanoparticles using a peptide barcoding method. I will also discuss my work engineering a previously reported RNA-encapsulating nanoparticle for RNA delivery in immortalized cell lines. Finally I will discuss my work combining knowledge from all of these efforts into the design of a novel non-porous protein nanoparticle that may provide an optimal scaffold for future efforts in nucleic acid delivery using protein nanoparticles.