Gene Editing Technique Successfully Used for First Time by Tel Aviv University to Treat Aggressive Metastatic Cancer in Mice

You shall serve Hashem your God, and He will bless your bread and your water. And I will remove sickness from your midst.

Exodus

23:

25

(the israel bible)

November 19, 2020

4 min read

A significant step on the way to finding a cure for some of the 500 cancers that plague mankind has been made by researchers at Tel Aviv University (TAU). The team, who worked on lab mice, showed that the CRISPR/Cas9 gene-editing system is very effective in treating metastatic cancers. 

 

The researchers developed a novel technology – a lipid nanoparticle-based delivery system that specifically targets cancer cells and neutralizes them genetically. This treatment causes permanent damage to cancer cells and potentially has no side effects, according to the TAU team, who have just published their findings in the prestigious Science Advances journal under the title “CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy.” The groundbreaking study was funded by ICRF (Israel Cancer Research Fund). 

 

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. As a result, the overall survival of mice with brain cancer was increased by 30%, and the survival rate of mice with metastatic ovarian cancer was increased by an astounding 80%.

 

The revolutionary work was conducted in the laboratory of Prof. Dan Peer, vice president for research and development and head of the Laboratory of Precision Nanomedicine at TAU’s Shmunis School of Biomedicine and Cancer Research. The impressive research was funded by ICRF (Israel Cancer Research Fund).

 

The research was conducted by Dr. Daniel Rosenblum together with doctoral student Anna Gutkin and colleagues at Peer’s laboratory, in collaboration with Dr. Dinorah Friedmann-Morvinski from TAU’s School of Neurobiology, Biochemistry and Biophysics; Dr. Zvi Cohen, director of the neurosurgical oncology unit and vice-chair of the department of neurosurgery at the Sheba Medical Center at Tel Hashomer (near Tel Aviv); Dr. Mark Behlke – chief scientific officer at IDT Inc. and his team, and Prof. Judy Lieberman of Boston Children’s Hospital and Harvard Medical School. 

 

CRISPR gene editing is a genetic engineering technique in molecular biology by which the genomes of living organisms can be modified. It is based on a simplified version of the bacterial CRISPRCas9 antiviral defense system. By delivering the Cas9 nuclease complexed with a synthetic guide RNA into a cell, the cell’s genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added in living organisms (in vivo).  

The technique is considered highly significant in biotechnology and medicine as it makes it possible for the genomes to be edited in vivo cheaply, easily and with great precision. It can be used in the creation of new medicines, agricultural products and genetically modified organisms or as a means of controlling pathogens and pests. It also has possibilities in the treatment of inherited genetic diseases as well as diseases arising from somatic mutations such as cancer. 

The development of the CRISPR gene-editing technique earned Jennifer Doudna and Emmanuelle Charpentier the Nobel Prize in Chemistry in 2020. 

  

To examine the feasibility of using the technology to treat cancer, 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 since diagnosis and a five-year survival rate of only three percent. 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%.

 

Ovarian cancer is a major cause of death among women and the most lethal cancer of the female reproductive system. Because it initially does not cause pain or other symptoms, most patients are diagnosed at an advanced stage of the disease when metastases have already spread throughout the body.  Despite progress in recent years, only a third of the patients survive this disease. But treatment with CRISPR-LNPs in a metastatic ovarian cancer mice model increased their overall survival rate by 80%. 

 

“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,” declared 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.”

 

“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,” he added. “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 explained that by demonstrating its potential in treating two aggressive cancers, the technology opens numerous new possibilities for treating other types of cancer as well as rare genetic diseases and chronic viral diseases such as AIDS. 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,” said 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, TAU’s technology transfer company, we are already negotiating with international corporations and foundations, aiming to bring the benefits of genetic editing to human patients.”

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