The CRISPR / Cas9 system is highly effective in the treatment of metastatic cancers

Reviewed by Emily Henderson, B.Sc.November 19, 2020

Tel Aviv University (TAU) researchers have shown that the CRISPR / Cas9 system is highly effective in treating metastatic cancers, a significant step on the road to finding a cure for cancer.

Researchers have developed a new 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 codes for the CRISPR Cas9 enzyme that acts as molecular scissors that cut through the DNA of cells.

The groundbreaking work was conducted in the laboratory of Prof. Dan Peer, VP for Research and Development and head of the Precision Nanomedicine Laboratory at the Shmunis School of Biomedicine and Cancer Research at TAU.

The research was conducted by Dr. Daniel Rosenblum together with Ph.D. student Anna Gutkin and colleagues from Prof. Peer’s laboratory, in collaboration with Dr. Dinorah Friedmann-Morvinski of the TAU School of Neurobiology, Biochemistry and Biophysics; Dr. Zvi R.

Cohen, Director of the Oncological Neurosurgery Unit and Vice President of the Department of Neurosurgery at Sheba Medical Center; Dr. Mark A. Behlke, Scientific Director of IDT Inc. and his team; and prof. Judy Lieberman of Boston Children’s Hospital and Harvard Medical School.

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

This is the first study in the world to show that the CRISPR genome editing system can be used to effectively treat cancer in a living animal. It should be emphasized that this is not chemotherapy. There are no side effects and a cancer cell treated in this way will never be active again. Cas9 molecular scissors cut the DNA of the cancer cell, neutralizing it and permanently preventing its replication. “

Dan Peer, Professor and Director, Precision Nanomedicine Laboratory, Shmunis School of Biomedicine and Cancer Research, Tel Aviv University

To examine the feasibility of using the technology to treat cancer, Prof. Peer and his team chose two of the deadliest cancers: glioblastoma and metastatic ovarian cancer.

Glioblastoma is the most aggressive type of brain cancer, with a life expectancy of 15 months after diagnosis and a five-year survival rate of only 3%. Researchers showed that a single CRISPR-LNP treatment doubled the average life expectancy of mice with glioblastoma tumors, improving their overall survival rate by approximately 30%.

Ovarian cancer is a leading cause of death among women and the deadliest cancer of the female reproductive system. Most patients are diagnosed with an advanced stage of the disease when the metastases have already spread throughout the body.

Despite the advances in recent years, only one third of patients survive this disease. Treatment with CRISPR-LNP in a mouse model with metastatic ovarian cancer increased their overall survival rate by 80%.

“CRISPR genome editing technology, capable of identifying and altering any genetic segment, has revolutionized our ability to individually interrupt, repair or even replace genes,” said Prof. Peer.

“Despite its wide use in research, clinical implementation is still in its infancy because an effective delivery system is needed to safely and accurately deliver CRISPR to its target cells. The delivery system we have developed targets responsible DNA. of the survival of cancer cells. This is an innovative treatment for aggressive cancers that today do not have effective treatments. “

The researchers note that by demonstrating its potential in treating two aggressive cancers, the technology opens up numerous new possibilities for treating other cancers, as well as rare genetic diseases and chronic viral diseases such as AIDS.

“We now intend to move on to experiments with blood cancers that are genetically very interesting, as well as genetic diseases such as Duchenne muscular dystrophy,” says prof. Peer. “It will likely take some time before the new treatment can be used in humans, but we are optimistic.

The entire scene of molecular drugs using messenger RNA (genetic messengers) is thriving – in fact, most COVID-19 vaccines currently under development are based on this principle. When we first talked about mRNA treatments 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, TAU’s Technology Transfer Company, we are already negotiating with international corporations and foundations, with the aim of bringing the benefits of gene editing to human patients. “