Remote-controlled gene therapy uses ultrasound to kill cancer

This is starting to get specific in its targeting.  Yet still a bit rough. At least we have a proof of concept.

doing all this in real life on a patient is likely a challenge.

all good to see though.

Remote-controlled gene therapy uses ultrasound to kill cancer

By Michael Irving

December 09, 2024

An artist's impression of CRISPR getting to work on cancer cells with the help of ultrasound pulses

Wang Lab and Pepper Workshop

A new kind of cancer gene therapy can be remotely activated at a specific part of the body. The team developed a version of CRISPR that responds to ultrasound, and demonstrated how it can be used to clear cancer in mice.

CRISPR is a powerful genetic editing tool that uses an enzyme called Cas9 to make precise edits to targeted genes. The problem is, it doesn’t always stay in the right part of the body, and can continue editing genes long after it’s needed, potentially triggering an immune response.

Now, scientists at the University of Southern California (USC) have demonstrated a new way to control when and where CRISPR does its work. In tests in mice, they used it to clear out cancer.

In practice, CRISPR could be incorporated into virus delivery vehicles and delivered intravenously to a patient. Then, focused ultrasound pulses can be directed at the desired part of the body, which activates the gene editing tool there and there alone. The trick is that the cells are designed to produce the Cas9 enzyme in response to heat, and that heat is induced by the ultrasound.

“In our controllable system, you can flip it on and off whenever you want,” said Peter Yingxiao Wang, co-lead author of the study. “As soon as you turn it on, the CRISPR molecule will start to do its job wherever you want it. Then, after a certain time, it will start to decay by itself, it will be shut down for a period, and then you can turn it on again whenever you want.”

To use this tool to fight cancer, the team set CRISPR to target telomeres, the repeating DNA sequences on the ends of chromosomes. This not only causes cancer cells to die off, but triggers an immune response that summons other cells to help finish off the tumors.

A third prong of attack comes from specialized CAR T cells. These are immune cells removed from a patient, tuned up to attack a specific target, and then reintroduced to the body. In this case, the target is a protein called CD19 which is expressed in high amounts by certain types of cancers. The kicker is that the team used CRISPR to ramp up production of CD19.

The team tested this combo treatment in mice with tumors under their skin. And sure enough, 100% of the mice receiving the CRISPR/CAR T cell therapy survived, clearing their cancers completely. By comparison, mice that received CAR T cell therapy alone saw a survival rate of just 40%.

While the results look promising, it’s obviously still early days for this treatment, and there’s no guarantee that the same benefits will carry across to humans. The team says that future work should focus on improving the technique and potentially extending it beyond CAR T cell therapy.