Systemic delivery of CRISPR-Cas9 nickase suppresses oncogene amplified cancer progression

Oncogene amplification is a key driver of tumorigenesis and a perpetuator of genomic instability. Oncogene amplification accelerates cancer cell proliferation and evolution, contributing substantially to the enhancement of adaptation mechanisms, such as treatment resistance, which pose a significant therapeutic challenge. However, previous studies have shown oncogene amplification to be a critical vulnerability, rendering cancer cells, but not normal cells, susceptible to targeted, CRISPR-Cas9 nickase – mediated DNA damage and cell death in vitro . Here, we demonstrate the initial framework for the translation of this potential therapeutic approach utilizing Cas9 ^D10A – mRNA and functionalized lipid nanoparticles for the targeted delivery, and suppression of disseminated MYCN -amplified neuroblastoma in vivo .