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Published on: September 5, 2018
Ultrasound Control of Genomic Regulatory Toolboxes for Cancer Immunotherapy
Yiqian Wu1,2, Ziliang Huang3,4, Yahan Liu5
1Shu Chien - Gene Lay Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA. yiqianwu@pku.edu.cn.
Focused ultrasound (FUS) controls CRISPR gene editing tools for precise cancer therapy. This technology primes tumors for CAR-T cell treatment by disrupting telomeres and activating immune cells non-invasively.
Area of Science:
- Biotechnology
- Molecular Biology
- Cancer Research
Background:
- CRISPR technologies require precise control for therapeutic applications.
- Focused ultrasound (FUS) offers deep tissue penetration and localized hyperthermia for transgene activation.
Purpose of the Study:
- To engineer inducible CRISPR-based tools controllable by FUS for precise genomic and epigenomic modulation.
- To demonstrate the efficacy of FUS-inducible CRISPR tools in cancer treatment models.
Main Methods:
- Development of FUS-inducible CRISPR, CRISPR activation (CRISPRa), and CRISPR epigenetic editor (CRISPRee).
- In vivo delivery of FUS-CRISPR using adeno-associated viruses (AAVs).
- FUS-mediated telomere disruption to prime solid tumors for CAR-T cell therapy.
Main Results:
- Demonstrated FUS-CRISPR tools' capability to modulate the genome and epigenome.
- FUS-CRISPR-mediated telomere disruption enhanced CAR-T cell therapy efficacy.
- In vivo studies showed FUS-CRISPR activating synNotch CAR-T cells to target tumor cells.
Conclusions:
- The FUS-CRISPR toolbox enables noninvasive, spatiotemporal control of genomic/epigenomic reprogramming.
- This technology holds promise for advanced cancer treatment strategies.
- FUS-inducible CRISPR offers a novel platform for precise therapeutic interventions.
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