Study shows CRISPR/Cas9 system can effectively treat metastatic cancers

Tel Aviv University researchers have shown that the advanced CRISPR/Cas9 system is extremely effective in curing metastatic cancers. This latest finding represents a major step towards finding a new treatment for cancer.

Image Credit: American Friends of Tel Aviv University.

The team designed an innovative lipid nanoparticle-based delivery system that particularly targets tumor cells and kills them through genetic manipulation. Called CRISPR-LNPs, the novel system carries a genetic messenger, also known as messenger RNA, which encodes for the CRISPR enzyme called Cas9. This enzyme serves as molecular scissors splicing the DNA of the cells.

The groundbreaking study was performed in the laboratory of Professor Dan 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 study was conducted by Dr. Daniel Rosenblum along with Ph.D. student Anna Gutkin and collaborators at Professor Peer’s laboratory, in association with Dr. Dinorah Friedmann-Morvinski from the School of Neurobiology, Biochemistry & Biophysics at Tel Aviv University.

The study also included 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 group; and Professor Judy Lieberman of Boston Children’s Hospital and Harvard Medical School.

The outcomes of the revolutionary study, which was financially supported by Israel Cancer Research Fund (ICRF), were published in the Science Advances journal in November 2020.

This is the first study in the world to prove that the CRISPR genome editing system can be used to treat cancer effectively in a living animal. 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.”

Dan Peer, Professor, VP for R&D, and Head of the Laboratory of Precision Nanomedicine, Shmunis School of Biomedicine and Cancer Research, Tel Aviv University

To investigate the possibility of applying the new technology to cure cancer, Professor Peer and his group selected two of the most aggressive cancers—that is, metastatic ovarian cancer and glioblastoma. Glioblastoma—the most aggressive form of brain cancer—has a life expectancy of 15 months following diagnosis, and has a five-year survival rate of just 3%.

The team showed that a single treatment with the CRISPR-LNPs system increased the average life expectancy of mice afflicted with glioblastoma tumors by two-fold, enhancing the animals’ overall survival rate by around 30%.

Ovarian cancer is a leading cause of death among the female population and is the deadliest cancer in women’s reproductive systems. A majority of the patients are diagnosed only at an advanced phase of the disease, especially when metastases have already spread all through the body.

In spite of advances made in the recent past, only one-third of the patients survive this cancer. The use of the CRISPR-LNPs system to treat a mice model of metastatic ovarian cancer boosted the overall survival rate by as much as 80%.

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.”

Dan Peer, Professor, VP for R&D, and Head of the Laboratory of Precision Nanomedicine, Shmunis School of Biomedicine and Cancer Research, Tel Aviv University

Professor Peer continued, “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 team also observed that by demonstrating its ability in treating the two deadliest forms of cancers, the new technology paves the way for many new possibilities for curing other types of cancer and also rare genetic disorders and chronic viral diseases, like AIDS.

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. 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.”

Dan Peer, Professor, VP for R&D, and Head of the Laboratory of Precision Nanomedicine, Shmunis School of Biomedicine and Cancer Research, Tel Aviv University

“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 TAU, we are already negotiating with international corporations and foundations, aiming to bring the benefits of genetic editing to human patients,” Professor Peer concluded.