CRISPR is a powerful gene-editing tool that uses an enzyme called Cas9 to precisely edit target genes. The problem is, it doesn't always stay in the right part of the body and can continue to edit genes long after it's needed, potentially triggering an immune response. A new cancer gene therapy can be activated remotely in specific parts of the body. The research team developed a CRISPR that responds to ultrasound waves and demonstrated how it could be used to clear cancer in mice.
Now, scientists at the University of Southern California (USC) have demonstrated a new way to control when and where CRISPR works. In experiments on mice, they used this method to eliminate cancer.
In practice, CRISPR could be incorporated into viral delivery vehicles and delivered intravenously to patients. Focused ultrasound pulses can then be applied directly to the desired part of the body, activating the gene-editing tool. The trick is that the cells are designed to produce the Cas9 enzyme when exposed to heat, which is induced by ultrasound waves.
"In our controllable system, you can turn it on or off at any time," said Peter Yingxiao Wang, co-first author of the study. "As soon as you turn it on, the CRISPR molecule starts working where you want it. Then, after a while, it starts to decay itself, shuts down for a while, and then you can always turn it back on again."
To harness this tool to fight cancer, the team set up CRISPR to target telomeres, the repetitive DNA sequences at the ends of chromosomes. Not only does this cause cancer cells to die, it also triggers an immune response that summons other cells to help destroy the tumor.
The third type of attack comes from specialized CART cells. These immune cells are removed from the patient, tuned to attack specific targets, and then reintroduced into the body. In this case, the target is a protein called CD19, which is expressed in large amounts by certain types of cancer. Most critically, the research team used CRISPR technology to increase CD19 production.
The team tested the combination therapy on mice with subcutaneous tumors. Sure enough, 100% of the mice receiving CRISPR/CART cell therapy survived and their cancer was completely eliminated. In comparison, mice receiving only CART cell therapy had a survival rate of only 40%.
While the results look promising, this therapy is clearly still in its early stages, and there's no guarantee that humans will experience the same benefits. The team says future work should focus on improving this technology and potentially expanding it beyond CART cell therapy.
The research results were published in the journal Nature Communications.