Researchers at Tel Aviv University have demonstrated that CRISPR gene editing can effectively eliminate head and neck tumors by directly injecting lipid nanoparticles (LNPs) carrying CRISPR components into tumors. In a study published in Advanced Science, they reported that 50% of treated tumors disappeared after 84 days, marking a significant advance in precision cancer therapy.
Gene editing to collapse cancer cells
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with poor survival rates due to treatment resistance and recurrence. The research team, led by Razan Masarwy, MD, PhD, and Dan Peer, PhD, sought to collapse the cancer structure by targeting SOX2, a gene essential for tumor survival.
“Our aim was to use genetic editing of a single gene expressed in this type of cancer to collapse the entire pyramid of the cancerous cell,” said Peer. “This gene is the cancer-specific SOX2, also expressed in other types of cancer, and overexpressed in these particular tumors.”
To deliver CRISPR components precisely to cancer cells, the team encapsulated Cas9 mRNA and guide RNA in lipid nanoparticles (LNPs) coated with an anti-EGFR antibody. “We targeted EGF because the cancer cells express the EGF receptor. Using our nano-lipid delivery system, we injected the drug directly into the tumor in a tumor model and successfully took out the gene—literally cutting it out from the cancer cell’s DNA with the CRISPR ‘scissors’.”
Tumor reduction and survival impact
The study found that:
- CRISPR treatment reduced tumor size by 90% in mice.
- Half of the tumors completely disappeared after 84 days.
- The treated mice had a 90% increase in survival.
Following three weekly injections of the CRISPR-LNP therapy, the researchers observed a “domino effect” leading to tumor regression. “We were happy to observe the domino effect we had predicted. Following three injections spaced one week apart, 50% of the cancerous tumors simply disappeared after 84 days—which did not happen in the control group.”
Expanding CRISPR cancer applications
This study builds on previous work from Peer’s team, who in 2020 were the first to use CRISPR to cut genes from cancer cells in mice. However, this is the first time they have applied the approach to head and neck cancers.
“Generally, CRISPR isn’t used for cancer because the assumption is that knocking out one gene wouldn’t collapse the whole pyramid. In this study, we demonstrated that there are in fact some genes without which a cancer cell cannot survive, making them excellent targets for CRISPR therapy.”
The team is now investigating whether additional genes may need to be cut for even stronger effects and expanding the approach to other cancers, including myeloma, lymphoma, and liver cancer.
