CRISPR technology effectively destroys metastatic cancer cells in living animals

Scientists at Tel Aviv University (TAU) report that the CRISPR / Cas9 system is effective in treating metastatic cancer, demonstrating an important step in finding a cure for cancer, they said. I am. Researchers have developed a lipid nanoparticle-based delivery system that specifically targets and disrupts cancer cells by genetic engineering. The CRISPR-LNPs system carries messenger RNA that encodes the CRISPR enzyme Cas9, which acts as a molecular scissors that cuts cellular DNA.

This work was carried out in the laboratory of Dr. Dan Peer, Vice President of R & D and Director of Precision Nanomedicine Research Institute at TAU’s Shmunis School of Biomedicine and Cancer Research. The study was conducted by Dr. Daniel Rosenbram, along with PhD student Anna Gatkin and peers and other collaborators in Pier’s lab.

the study “CRISPR-Cas9 genome editing with targeted lipid nanoparticles for cancer treatmentIs displayed in Science Advances..

“The use of CRISPR-Cas9 technology for cancer treatment has been hampered by the inefficiency of tumor editing and the potential toxicity of existing delivery systems. Here we use Cas9 mRNA and new aminoionic lipids. Describes safe and efficient lipid nanoparticles (LNPs) for the delivery of sgRNA, “the researchers write.

“A single intracerebral injection of CRISPR-LNP (sgPLK1-cLNP) for PLK1 into aggressive orthotopic glioblastoma allows up to 70% gene editing in vivo, causing tumor cell apoptosis. CLNP was also designed for antibody-targeted delivery to reach disseminated tumors, suppressing tumor growth by 50% and improving survival by 30%. EGFR-targeted sgPLK1-cLNP Intraperitoneal injection caused selective uptake into disseminated ovarian tumors, allowed up to 80% gene editing in vivo, inhibited tumor growth, and increased survival by 80%.

“The ability of tumors to disrupt gene expression in vivo opens new avenues for the treatment and research of cancer and opens up potential applications for target gene editing in non-cancerous tissues.”

“This is the world’s first study to demonstrate that the CRISPR genome editing system can be used to effectively treat cancer in living animals,” Peer said. “It should be emphasized that this is not chemotherapy. There are no side effects and cancer cells treated in this way will never be active again. Cas9 molecular scissors cut the DNA of the cancer cells, thereby It neutralizes it and prevents replication forever. “

To investigate the feasibility of treating cancer using this technique, Peer and his team selected two of the most deadly cancers, glioblastoma and metastatic ovarian cancer. Glioblastoma is the most aggressive type of brain tumor, with a life expectancy of 15 months after diagnosis and a 5-year survival rate of only 3%. Researchers have demonstrated that a single treatment with CRISPR-LNP doubles the life expectancy of mice with glioblastoma tumors and improves overall survival by about 30%.

Ovarian cancer is the leading cause of death in women and the most deadly cancer in the female reproductive system. Most patients are diagnosed at an advanced stage of the disease, where metastases have already spread throughout the body. Despite recent advances, only one-third of patients survive the disease. Treatment with CRISPR-LNP in a mouse model of metastatic ovarian cancer increased their overall survival by 80%.

“CRISPR genome editing technology that can identify and modify any gene segment has revolutionized our ability to disrupt, repair, and even replace genes in a personalized way,” continued Peer. “Despite its widespread use in research, clinical implementation is still in its infancy because an effective delivery system is needed to deliver CRISPR safely and accurately to target cells. Delivery systems target DNA that is involved in the survival of cancer cells. This is an innovative treatment for invasive cancer for which there is no effective treatment today. “

By demonstrating its potential in the treatment of two aggressive cancers, researchers treat not only other types of cancer, but also rare genetic and chronic viral diseases such as AIDS. It states that it opens up many new possibilities for.

“We are now going to experiment with genetically very interesting blood cancers and genetic diseases such as Duchenne muscular dystrophy,” Peer explained. “It will probably take some time for new therapies to be available to humans, but we are optimistic. The entire molecular drug scene using messenger RNA is thriving … in fact, most. COVID-19 (New Coronavirus Infection) (# If there is no character limit, add parentheses when it first appears Vaccines currently under development are based on this principle. “

“When we first talked about treatment with mRNA 12 years ago, people thought it was a science fiction. In the near future, many genetic messenger-based treatments for both cancer and genetic diseases. I believe there will be personalized treatments. Through TAU’s technology transfer company Ramot, we are already negotiating with international companies and foundations to bring the benefits of genetic editing to human patients. We aim to bring it. “