A revolutionary CRISPR-based gene therapy has shown impressive results in cell and mouse models, according to a study published in Science Advances. After just one injection of the nanoparticle-directed therapy, the average survival rate within one cancer model group was improved by 30 percent on average, while another with a different form of cancer received a boost of 80 percent.
“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 Professor Dan Peer, head of the Laboratory of Precision Nanomedicine at the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University, in a statement. “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.”
CRISPR-Cas9 genetic editing has taken the medical world by storm since its debut in 2012, with the ability to directly target specific regions of DNA and either insert a desired sequence or fix a pathogenic mutation. CRISPR contains a small piece of RNA (single-stranded DNA) that guides Cas9 to a target location before Cas9 goes to work on the region by cutting the double-stranded DNA. The DNA will then get repaired, incorporating the new sequence designed by the researchers in the process.
But how can this be utilized to combat cancer? Up until now, it wasn’t feasible. Previous attempts could not identify a delivery vector, which is the molecule the CRISPR-Cas9 system is carried in, that did not have potential to harm normal cells – and even if they did target the cancer cells, the amount of DNA edited by the system was low.
However, by packaging the system into novel lipid nanoparticles (LNPs), the researchers believe they have found the answer. By inhibiting a gene (PLK1) involved in the cell cycle, the researchers hoped to disrupt the uncontrolled cell division and therefore prevent tumor growth. To test their new method, the team performed genetic editing on cell cultures and live animals with two types of extremely aggressive and deadly cancers: glioblastoma (cancer within the brain or spinal cord) and metastatic ovarian cancer. Both cancers typically have poor survival rates, with just 3 percent of glioblastoma patients and 17 percent of ovarian cancer patients surviving after five years.
Once the CRISPR-LNPs were injected into glioblastoma mouse models, tumor growth saw a reduction of 50 percent, and the animals had an improved survival rate of 30 percent over the 60-day test period. This represents the largest increase in glioblastoma survival rate of a single treatment therapy that has ever been demonstrated.
On mice with ovarian cancer, the treatment had even more benefit – it increased the survival rate by 80 percent.
It is important to note these results are preliminary studies in animal and cell models, and as such do not necessarily translate to humans. Alongside this, the mouse control and test groups – while significant – consisted of eight mice each, so further study will be required to confirm if the survival rate is consistent across larger samples.
The researchers are not stopping at cancer and believe their technology has the potential to help a variety of genetic conditions.
“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.”