Thursday, December 26, 2024

Remote-controlled gene therapy uses ultrasound to kill cancer

Good news! Amazing stuff! Cancer is history (soon)!

"... The resulting toolkit will allow CRISPR gene editing to be precisely targeted to the specific areas requiring treatment. The research team is already applying this discovery to refine their work in cancer immunotherapy. ...

But we are pushing it one step further to make it controllable. 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.” ...

focused ultrasound as part of groundbreaking cancer immunotherapy research using engineered Chimeric Antigen Receptor (CAR) T-cells — immune cells that are extracted from patients and modified to be more effective against cancer. ... team harness ultrasound waves to directly control these CAR T-cells for precision targeting of tumor cells without harming healthy tissue. ...

“This is the first study that provides a very comprehensive, ultrasound-controllable CRISPR toolbox to knock out, activate, or silence a specific gene,” ...

“The telomere has many, many repeats, and we use CRISPR, guided by ultrasound, to cut this telomere so that it will trigger the chromosome to be cut off at two ends,”  ... “Because they have a repeatable sequence, they will all be cut, and therefore, the tumor cell can no longer repair itself. It’s all broken. The cell will then undergo apoptosis and die.” ..."

From the abstract:
"There remains a critical need for the precise control of CRISPR (clustered regularly interspaced short palindromic repeats)-based technologies. Here, we engineer a set of inducible CRISPR-based tools controllable by focused ultrasound (FUS), which can penetrate deep and induce localized hyperthermia for transgene activation. We demonstrate the capabilities of FUS-inducible CRISPR, CRISPR activation (CRISPRa), and CRISPR epigenetic editor (CRISPRee) in modulating the genome and epigenome. We show that FUS-CRISPR-mediated telomere disruption primes solid tumours for chimeric antigen receptor (CAR)-T cell therapy. We further deliver FUS-CRISPR in vivo using adeno-associated viruses (AAVs), followed by FUS-induced telomere disruption and the expression of a clinically validated antigen in a subpopulation of tumour cells, functioning as “training centers” to activate synthetic Notch (synNotch) CAR-T cells to produce CARs against a universal tumour antigen to exterminate neighboring tumour cells. The FUS-CRISPR(a/ee) toolbox hence allows the noninvasive and spatiotemporal control of genomic/epigenomic reprogramming for cancer treatment."

Remote-controlled gene therapy uses ultrasound to kill cancer

New CRISPR Toolkit to Allow Remote-Controlled Genome Editing (original news release) "USC Viterbi biomedical engineers harness focused ultrasound to revolutionize CRISPR’s capabilities to treat countless diseases."



Fig. 4: FUS-CRISPR-mediated telomere disruption can inhibit tumor cell growth and its resistance to CAR-T cell killing.


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