A novel lipid nanoparticle-based delivery system was developed that specifically targets cancer cells and destroys them with genetic manipulation. CRISPR-LNPs carries a genetic messenger RNA which encodes for the CRISPR enzyme Cas9 which acts as molecular scissors that cut the cells’ DNA. Results from this groundbreaking study are published in Science Advances.
“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, VP for R&D and Head of the Laboratory of Precision Nanomedicine at the Shmunis School of Biomedicine and Cancer Research at TAU. “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.“
Glioblastoma and metastatic ovarian cancer were chosen to examine the feasibility of the technology to treat cancer. Glioblastoma is the most aggressive form of brain cancer with life expectancy being only 15 months after diagnosis and a 5-year survival rate of 3%. Ovarian cancer is a major cause of death among women and the most lethal form of female reproductive system cancer with most being diagnosed at an advanced stage of disease when metastases have already spread throughout the body and only one-third of patients survive the disease.
A single treatment with CRISPR-LNPs was demonstrated to double the average life expectancy of mice with glioblastoma tumors, improving the overall survival rate by 30%; while treatment with CRISPR-LNR in metastatic ovarian cancer mouse models increased the overall survival rate by 80%. It was noted that by treating both aggressive cancers this technology opens paths to numerous new possibilities for treating other types of cancers along with rare genetic diseases and chronic viral diseases.
“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,” 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.“
“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,” says 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 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, 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.”
