Researchers from Tel Aviv University utilized CRISPR to cut a single gene from cancer cells of head and neck tumors – and successfully eliminated 50% of the tumors in model animals. This groundbreaking study was led by Dr. Razan Masarwy, MD, Ph.D. from the lab of  Prof. Dan Peer - a global pioneer in mRNA-based drugs, Director of the Laboratory of Precision Nanomedicine, VP for Research and Development and member of the Shmunis School of Biomedicine and Cancer Research – all at TAU. The findings were published in the prestigious journal Advanced Science.

A New Approach to Treating Head and Neck Cancers

“Head and neck cancers are prevalent, ranking fifth in cancer mortality”, says Prof. 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. We aimed 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”.

Prof. Dan Peer.

Prof. 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 Prof. 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 - 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”.

Prof. Dan Peer & research team.

TAU Pioneers CRISPR for Cancer Treatment

In 2020, Prof. Peer and his team were the first in the world to use CRISPR to cut genes from cancer cells in mice and 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. In this study we demonstrated that there are 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, or perhaps not. 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 (under grant agreement # 825828), and the Shmunis Fund for gene editing.

The research was led by the lab team of Prof. Yossi Yovel from the School of Zoology in the Wise Faculty of Life Sciences and the Steinhardt Museum of Natural History at Tel Aviv University. The study included contributions from Dr. Maya Weinberg, Dean Zigdon, and Mor Taub, and was published in the scientific journal BMC Biology.

Prof. Yossi Yovel.

Over three years, the researchers monitored ten bat colonies in urban and rural areas, sampling hundreds of female bats and approximately 120 pups from these colonies. The findings revealed that pups born in urban colonies were, on average, 2.5 weeks older, as evidenced by their longer forearms and higher body weights compared to pups from rural colonies.

Prof. Yovel explains: “Fruit bats living in cities benefit from favorable environmental conditions, including higher temperatures due to the ‘urban heat island’ effect and greater food availability, primarily from ornamental fruit trees irrigated year-round. These conditions allow urban bats to cope better with harsh winters and start their reproductive cycles earlier. This enables females to give birth earlier in the season, increasing their chances of becoming pregnant again within the same year.”

However, the researchers emphasize that it remains unclear whether the bats are shortening their pregnancies (a capability known in some bat species) or becoming pregnant earlier. They add that the study opens the door to further research on how urbanization affects mammalian reproductive patterns in general and bats in particular, and how these findings can be used to protect other species in changing ecosystems. “This study highlights the importance of understanding the connection between animals and their environments, especially in an era when urbanization is reshaping the planet,” concludes Prof. Yovel.

A mother bat in flight, carrying her pup beneath her in the city and countryside (Photo credit: Yuval Barkai).

The study, led by Dr. Omri Bronstein from the School of Zoology at Tel Aviv University’s Wise Faculty of Life Sciences and the Steinhardt Museum of Natural History, was published in the prestigious journal Ecology.

The Research Team. Photo credit: Tel Aviv University.

“This is a first-rate ecological disaster”, explains Dr. Bronstein.

She continues: “Sea urchins are vital to the health of coral reefs. They act as the ‘gardeners’ of the reef by feeding on algae, preventing it from overgrowing and suffocating the coral, which competes with algae for sunlight. In 1983, a mysterious disease wiped out most of the Diadema sea urchins in the Caribbean. Unchecked, the algae there proliferated, blocking sunlight from the coral, and the region shifted from a coral reef ecosystem to an algae-dominated one. Even 40 years later, the sea urchin population — and consequently the reef — has not recovered”.

In 2022, the disease reemerged in the Caribbean, targeting the surviving sea urchin populations and individuals. This time, armed with advanced scientific and technological tools to collect and interpret the forensic evidence, researchers at Cornell University successfully identified the pathogen as a ciliate Scuticociliate parasite. A year later, in early 2023, Dr. Bronstein was the first to identify mass mortality events among long-spined sea urchins, a close relative of the Caribbean Sea urchins, in the Red Sea.

Sea urchin mortalities on Reunion Island. Photo credit: Jean-Pascal Quod.

“Until recently, this was one of the most common sea urchins in Eilat’s coral reefs — the familiar black urchins with long spines,” says Dr. Bronstein. “Today, this species no longer exists in significant numbers in the Red Sea. The event was extremely violent: within less than 48 hours, a healthy population of sea urchins turned into crumbling skeletons. In some locations in Eilat and the Sinai, mortality rates reached 100 percent. In follow-up research, we demonstrated that the Caribbean pathogen was the same one affecting populations in the Red Sea”.

Genetic Proof Links Global Sea Urchin Deaths to One Pathogen

Now, using genetic tools, Dr. Bronstein and his international colleagues have shown that the same ciliate parasite is responsible for similar mortality events off the coast of Réunion Island in the Indian Ocean. “This is the first genetic confirmation that the same pathogen is present in all these locations,” he says. “Now it’s a global event, a pandemic. The Caribbean, Red Sea, and the Indian Ocean are critical regions for the world’s coral reefs, and mortality rates for sea urchins in these areas are very high — over 90 percent. As of now, we have no evidence of this pathogen in Pacific Ocean sea urchins, but this is something we are actively investigating. Although we’ve developed genetic tools for the specific identification of the pathogen, it’s difficult to monitor such rapid extinction events in the vast underwater environment. We are terrestrial creatures, and some reefs are located in deep or remote areas. If we miss the mortality event by even a couple of days, we might find no trace of the extinct population”.

 Four healthy sea urchin species on Reunion Island. Photo credit: Jean-Pascal Quod.

To track the progression of the pandemic, Dr. Bronstein has established an international network of collaborators. He provides them with alerts about the likelihood of mortality events in their regions and sends them the necessary equipment to sample and preserve affected sea urchins for comparison with samples from other locations. These kits are then sent back to the laboratory at Tel Aviv University.

“For populations that are already infected, we really have no tools to help them,” says Dr. Bronstein with regret. “There is no Pfizer or Moderna for sea urchins — not because we don’t want one, but because we simply can’t treat them underwater. Our focus must be on two entirely different tracks. The first is prevention. To prevent further spread of the pandemic, we need to understand why it erupted here and now. We’ve developed two hypotheses for this. The first is the transportation hypothesis — that the pathogen from the Caribbean was transported by humans to new and distant regions after being carried in the ballast water of ships, infecting sea urchins in the Red Sea before spreading to the Western Indian Ocean.

The sea urchin Diadema setosum before (left) and after (right) mortality. The white skeleton is exposed following tissue disintegration and loss of spines. Photo credit: Tel Aviv University.

How climate change might be spreading marine diseases worldwide

Incidentally, if this hypothesis is correct, we would expect to see mortality events in West Africa as well — as many cargo ships from the Caribbean stop there on their way to the Mediterranean and then through the Suez Canal to the Red Sea. Indeed, just in the past few weeks, we’ve discovered widespread mortality events in West Africa, as we predicted, and we’ve managed to obtain a limited number of samples collected during these events, which we are currently analyzing in the lab. If ships are indeed the source of the spread, then we could think of mitigation strategies. It’s not simple, and ships will never be completely sterile, but there are measures we can take. The second possibility is even more concerning: that the pathogen has always been present, and climatic changes have triggered its virulence and outbreak. That’s a challenge of an entirely different magnitude, one that we, as marine biologists, have very limited means to address”.

In parallel with global efforts, Dr. Bronstein has recently established a breeding nucleus for the affected sea urchins at the Israel Aquarium in Jerusalem, in collaboration with the Biblical Zoo and the Israel Nature and Parks Authority. This breeding population will serve as a reserve to restore affected populations and advance research into infection mechanisms and possible treatments.

“The pathogen is transmitted through water, so even sea urchins raised for research purposes in aquariums at the Interuniversity Institute for Marine Sciences and the Underwater Observatory in Eilat became infected and died. That is why we established a breeding nucleus with the Israel Aquarium, whose aquariums are completely disconnected from seawater. We genetically test the urchins transferred to the nucleus to ensure they are not carriers of the disease and that they genetically belong to the Red Sea population, enabling us to rehabilitate the population in the future. At the same time, we are using them to develop sensitive genetic tools for early disease detection from seawater samples — essentially creating ‘underwater COVID tests’ for sea urchins”.