Development of a New Therapeutic Approach Based on Peptide Nanoparticles Delivering CRISPR-Cas9 for the Specific Targeting of KRAS Mutations

This study presents a novel therapeutic approach using peptide-based nanoparticles (PBN) to deliver CRISPR-Cas9 for targeting KRAS mutations, specifically G12D and G12V, which are prevalent in pancreatic and colorectal cancers. The PBN system effectively forms stable complexes with CRISPR-Cas9 components, protecting them from degradation and facilitating intracellular delivery. The study demonstrated a 60% gene editing efficiency for the luciferase gene and successfully targeted KRAS mutations with 20% efficiency for G12D and 60% for G12V, leading to reduced phosphorylation of downstream signaling proteins and restored cell proliferation rates. These findings highlight the potential of PBN as a promising non-viral delivery system for CRISPR-Cas9, offering new therapeutic avenues for targeting KRAS mutations in cancer.