Focused Ultrasound Enhances CRISPR Precision for Genetic Disorder Treatment
Key Insights
Researchers have developed an ultrasound-controlled CRISPR (search) system for precise gene editing, enhancing control over gene activation and silencing.
The new method uses focused ultrasound to initiate temperature changes at specific sites, activating CRISPR (search) proteins for targeted DNA modification.
Combining focused ultrasound-enabled CRISPR (search) with CAR T-cell therapy demonstrated enhanced tumor eradication in mouse studies, showing promising results.
USC Viterbi School of Engineering researchers have developed an innovative update to CRISPR (search) technology, integrating focused ultrasound to achieve unprecedented precision in treating genetic disorders and diseases. This advancement allows for targeted gene editing in specific areas, offering enhanced control over when and where CRISPR is activated.
How it Works
The new system uses focused ultrasound waves to initiate a temperature change at the precise site where researchers want the CRISPR (search) protein to activate. This allows for controlled activation and deactivation of the gene-editing function, addressing a key limitation of traditional CRISPR methods.
"CRISPR (search) is revolutionary," said Peter Yingxiao Wang, Dwight C. and Hildagarde E. Baum Chair in Biomedical Engineering. "Instead of continuously editing the genome, we can now control it to be activated at a specific location and at a specific time using a non-invasive remote-controlled ultrasound wave. That's the breakthrough."
Longwei Liu, assistant professor of biomedical engineering, added, "In our controllable system, you can flip it on and off whenever you want. So that's the beauty of the system – providing another layer or controllability, and therefore precision."
Application in Cancer Immunotherapy
The research team demonstrated the power of focused ultrasound-enabled CRISPR (search) in cancer (search) immunotherapy. By targeting the telomere (search), a DNA-protein structure protecting chromosome integrity, they induced tumor cell apoptosis. The focused ultrasound-enabled CRISPR cuts the telomere, triggering chromosome damage that the tumor cell cannot repair.
"The telomere (search) has many, many repeats, and we use CRISPR (search), guided by ultrasound, to cut this telomere so that it will trigger the chromosome to be cut off at two ends," Wang explained. "Because they have a repeatable sequence, they will all be cut, and therefore, the tumor cell can no longer repair itself... The cell will then undergo apoptosis and die."
Following telomere (search) disruption, the dying tumor cells release cytokines, attracting other immune cells to attack the remaining tumor cells. The team further enhanced the cancer (search)-killing effect by using SynNotch CAR T-cells (search), engineered to target cancer cells expressing the CD19 (search) protein, which the CRISPR (search) tool activates. This combined approach creates a "training center" on the tumor surface, enhancing the CAR T-cells' ability to target the entire tumor population.
Promising Results in Mouse Studies
The research team reported promising results from mouse studies using the combined focused ultrasound CRISPR (search) and CAR T-cell technology.
"In all the mice, the tumor was not only slowing in growth, but it also got cleared - the tumor essentially decayed and disappeared. So, these are very encouraging results," Wang said.
Potential Applications
This technology holds potential for treating a wide range of genetic disorders, diseases, and autoimmune conditions. The ability to precisely control CRISPR (search) activation offers a significant advantage over existing methods, reducing the risk of off-target effects and immunogenicity.
The study, published in Nature Communications, was authored by Yiqian Shirley Wu, Peixiang He, and collaborators at UC San Diego, Georgia Institute of Technology, and Emory University.