Researchers Developing Cancer Treatment by Genetic Manipulation

Researchers at Tel Aviv University announced on Thursday a significant advance in treating metastatic cancers by means of genetic manipulation.

The CRISPR/Cas9 system was found to be very effective. It uses a novel technology – a lipid nanoparticle-based delivery system that specifically targets cancer cells and destroys them by genetic manipulation. The system, called CRISPR-LNPs, carries a genetic messenger (messenger RNA), which encodes for the CRISPR enzyme Cas9 that acts as molecular scissors that cut the cells’ DNA.

To examine the feasibility of using the technology, Prof. Dan Peer and his team at Tel Aviv University chose one of the deadliest cancers: glioblastoma. Glioblastoma is the most aggressive type of brain cancer, with a life expectancy of 15 months since diagnosis and a five-year survival rate of only 3%. The researchers demonstrated that a single treatment with CRISPR-LNPs doubled the average life expectancy of mice with glioblastoma tumors, improving their overall survival rate by about 30%.

“This is the first study in the world to prove that the CRISPR genome editing system can be used to treat cancer in a living animal effectively,” says Prof. Peer. “It must be emphasized that this is not chemotherapy. There are no side effects, and a cancer cell treated in this way will never become active again. The molecular scissors of Cas9 cut the cancer cell’s DNA, thereby neutralizing it and permanently preventing replication.”

Prof. Peer adds: “The CRISPR genome editing technology, capable of identifying and altering any genetic segment, has revolutionized our ability to disrupt, repair or even replace genes in a personalized manner. But despite its extensive use in research, clinical implementation is still in its infancy because an effective delivery system is needed to safely and accurately deliver the CRISPR to its target cells. The delivery system we developed targets the DNA responsible for the cancer cells’ survival. This is an innovative treatment for aggressive cancers that have no effective treatments today.”

The researchers note that by demonstrating its potential in treating an aggressive cancer, the technology opens numerous new possibilities for treating other types of cancer as well as rare genetic diseases and chronic viral diseases. It should be noted that a similar technology of mRNA is used for Corona vaccines by Moderna and Pfizer (BioNTech).

“We now intend to go on to experiments with blood cancers that are very interesting genetically, as well as genetic diseases such as Duchenne muscular dystrophy,” says Prof. Peer.

“It will probably take some time before the new treatment can be used in humans, but we are optimistic. The whole scene of molecular drugs that utilize messenger RNA (genetic messengers) is thriving – in fact, most COVID-19 vaccines currently under development are based on this principle.

“When we first spoke of treatments with mRNA twelve years ago, people thought it was science fiction. I believe that in the near future, we will see many personalized treatments based on genetic messengers – for both cancer and genetic diseases. Through Ramot, the Technology Transfer Company of Tel Aviv University, we are already negotiating with international corporations and foundations, aiming to bring the benefits of genetic editing to human patients.”

The work was conducted in the laboratory of Prof. Peer, VP for R&D and Head of the Laboratory of Precision Nanomedicine at the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University. The research was conducted by Dr. Daniel Rosenblum together with Ph.D. student Anna Gutkin and colleagues at Prof. Peer’s laboratory, in collaboration with Dr. Dinorah Friedmann-Morvinski from the School of Neurobiology, Biochemistry & Biophysics at TAU, Dr. Zvi R. Cohen – Director of the Neurosurgical Oncology Unit and Vice-Chair of the Department of Neurosurgery at the Sheba Medical Center, Dr. Mark A. Behlke – Chief Scientific Officer at IDT Inc. and his team, and Prof. Judy Lieberman of Boston Children’s Hospital and Harvard Medical School.

The results of the groundbreaking study, which was funded by ICRF (Israel Cancer Research Fund), were published in November 2020 in the Science Advances journal.