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CRISPR-based treatment destroys two cancer types

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23rd November 2020

CRISPR-based treatment destroys two cancer types

Researchers at Tel Aviv University (TAU) in Israel have demonstrated that the CRISPR/Cas9 genome editing system is very effective in treating brain and ovarian cancers, without side effects.

 

 

Scientists at Tel Aviv University (TAU) have developed a lipid nanoparticle-based delivery system that specifically targets cancer cells and destroys them by genetic manipulation. This novel system, which they call CRISPR-LNPs, carries a genetic messenger (messenger RNA), which encodes for the CRISPR enzyme Cas9 that acts as molecular scissors to cut the cells’ DNA.

CRISPR-Cas9 made its debut in 2012. Since then, it has shown great potential with its ability to precisely target sections of DNA and either edit or replace the defective parts. However, using this method against cancer has been problematic. Previous attempts have either been unable to identify a suitable delivery vector without harming normal cells, or the amount of DNA edited was too low. The new lipid nanoparticle created at TAU appears to be a major step forward in overcoming these issues.

“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,” said Prof. Dan Peer, Head of TAU’s Laboratory of Precision Nanomedicine. “It must be emphasised 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, neutralising it and permanently preventing replication.”

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To examine the feasibility of their technology, 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 just 15 months after 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 tumours and improved their overall survival rate by 30%. Ovarian cancer, meanwhile, is a major cause of death among women and the most lethal cancer of the female reproductive system. Most patients are diagnosed at an advanced stage, when metastases have already spread throughout the body. Despite progress in recent years, only a third of the patients survive this disease. Treatment with CRISPR-LNPs in a metastatic ovarian cancer mice model increased their overall survival rate by 80%.

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“The CRISPR genome editing technology, capable of identifying and altering any genetic segment, has revolutionised our ability to disrupt, repair or even replace genes in a personalised manner,” said Prof. Peer. “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.”

Having demonstrated its potential in treating two aggressive cancers, the team at TAU believe their technology opens numerous new possibilities for treating other types of cancer, as well as rare genetic diseases and chronic viral diseases such as AIDS.

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“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 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 utilise messenger RNA 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 personalised 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.”

The results of this groundbreaking new study, which was funded by the Israel Cancer Research Fund (ICRF), appear this month in the peer-reviewed journal Science Advances.

 

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