Spotlight Publication: “Non-Viral In Vivo Delivery of CRISPR-Cas9 using Protein-Agnostic, High-Loading Porous Silicon and Polymer Nanoparticles” published in ACS Nano
“Non-Viral In Vivo Delivery of CRISPR-Cas9 using Protein-Agnostic, High-Loading Porous Silicon and Polymer Nanoparticles” published in ACS Nano, selected as VINSE Spotlight Publication.
This research, led by Biomedical Engineering Prof. Craig Duvall and his 2023 PhD graduate Brock Fletcher, was recently published in ACS Nano. This interdisciplinary project involved several other VINSE labs (Weiss, Brunger, and Batista) in addition to external collaboration with the Gersbach Lab at Duke. The authors sought an engineering solution to address a central problem in medicine: delivery of gene-editing proteins to diseased tissues in vivo. The authors hypothesized that Porous Silicon Nanoparticles (PSiNPs) may have unique advantages in solving this problem. Specifically, PSiNPs were found to load ultra-high levels of proteins regardless of the specific characteristics (size and charge) of the protein. In practice, the platform nature of PSiNPs enabled their facile adaptation for delivery of gene editing ribonucleoprotein complexes, which comprise both protein and nucleic acid components. The cargo agnostic nature makes PSiNPs amenable to co-loading of these two cargoes which have distinct properties. In the work, a polymeric coating was also optimized for improving the stability of the particles and helping them to deliver the gene editing ribonucleoproteins into the cellular nucleus (where genomic DNA is located). This system was developed, optimized, and applied in this work successfully for gene editing within cells in culture and in vivo in animal models of arthritis and muscular dystrophy.