Researchers from Tel Aviv University (TAU) used the genetic editing tool CRISPR to cut a single gene from cancer cells of head and neck tumors, which successfully eliminated 50% of the tumors in model animals.

This groundbreaking study was led by Dr. Razan Masarwy, MD, PhD, from the lab of Professor Dan Peer. Professor Peer is a global pioneer in mRNA-based drugs, the Director of the Laboratory of Precision Nanomedicine, the VP for Research and Development, and a member of the Shmunis School of Biomedicine and Cancer Research, all at TAU. The findings were published on December 30, 2024, in the journal Advanced Science.

“Head and neck cancers are very common, ranking fifth in cancer mortality,” says Professor Peer. “These are localized cancers, typically starting in the tongue, throat, or neck, which can later metastasize. If detected early, localized treatment can effectively target the tumor.

“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. This gene is the cancer-specific SOX2, also expressed in other types of cancer, and overexpressed in these particular tumors.”

Professor Peer and his colleagues are global pioneers in developing mRNA-based drugs encased in synthetic lipid particles that mimic biological membranes. In this study, the researchers synthesized special lipids that encapsulate the delivered CRISPR system in an RNA format. An antibody targeting a receptor against a protein named EGF was attached to the surface of these particles.

“These tumors are highly targeted,” explains Professor Peer. “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.’

“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.”

In 2020, Professor Peer and his team were the first in the world to use CRISPR to cut genes from cancer cells in mice and in a cell-specific manner, and this is the first time they have applied it 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,” Professor Peer says. “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. Since cancer cells sometimes compensate with other genes, it’s possible that additional genes need to be cut out.

“Theoretically, this approach could be effective against many types of cancer cells, and we are already working on additional cancer types, including myeloma, lymphoma, and liver cancer.”

This study was supported in part by the EXPERT project (European Union’s Horizon 2020 research and innovation programme), and the Shmunis Fund for gene editing.