CRISPR/Cas9 gene editing boosts effectiveness of ultrasound cancer
therapy

Date:
December 8, 2021
Source:
American Chemical Society
Summary:
Sonodynamic therapy uses ultrasound in combination with drugs
to release harmful reactive oxygen species (ROS) at the site
of a tumor. However, the treatment isn't very effective because
cancer cells can activate antioxidant defense systems to counteract
it. Now, researchers have breached these defenses with CRISPR/Cas9
gene editing, allowing sonodynamic therapy to effectively shrink
tumors in a mouse model of liver cancer.



FULL STORY ========================================================================== Sonodynamic therapy uses ultrasound in combination with drugs to release harmful reactive oxygen species (ROS) at the site of a tumor. However,
the treatment isn't very effective because cancer cells can activate antioxidant defense systems to counteract it. Now, researchers reporting
in ACS Central Sciencehave breached these defenses with CRISPR/Cas9 gene editing, allowing sonodynamic therapy to effectively shrink tumors in
a mouse model of liver cancer.


========================================================================== Hepatocellular carcinoma, the most common form of liver cancer, has a
poor prognosis, and surgical treatment by removing part of the liver
or transplanting a healthy liver is not suitable for patients with more advanced disease. Because ultrasound can penetrate deep within tissues, sonodynamic therapy could be an effective, non-invasive way to treat hepatocellular carcinoma. But currently, cancer cells can quickly overcome
the therapy by activating a gene called nuclear factor erythroid 2-related factor 2 (NFE2L2), which deploys the cells' detoxification and antioxidant enzyme defenses.

CRISPR/Cas9 gene-editing technology has been used to knock down gene
expression in the lab. So, Wei Feng, Huixiong Xu, Yu Chen and colleagues wondered if they could increase sonodynamic therapy's effectiveness by
using this technology to reduce NFE2L2 expression.

As a first step, the researchers encapsulated the CRISPR/Cas9 system
and an ROS precursor molecule in lipid nanoparticles. Then, they treated hepatocellular carcinoma cells in a petri dish with the nanoparticles. The lipid nanoparticles were taken up by the cells' lysosomes. Ultrasound
treatment caused ROS formation, which ruptured lysosomes and allowed
the CRISPR/Cas9 system to enter the nucleus and knock down NFE2L2gene expression. The ROS also damaged other cellular components. As a result, significantly more cancer cells died from the sonodynamic therapy than
without NFE2L2gene editing.

Next, the team injected the nanoparticle treatment into mice with
implanted human hepatocellular carcinoma tumors. After 15 days
of the combined nanoparticle and ultrasound treatment, all of the
tumors in the mice disappeared and didn't come back. Mice treated with sonodynamic therapy alone had fewer tumors than untreated mice, but the addition of the CRISPR/Cas9 system significantly improved the therapy's effectiveness. Because gene editing occurs only in tumor tissues under ultrasound irradiation, it won't cause gene mutations in healthy tissues,
the researchers say.

========================================================================== Story Source: Materials provided by American_Chemical_Society. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Haohao Yin, Liping Sun, Yinying Pu, Jifeng Yu, Wei Feng, Caihong
Dong,
Bangguo Zhou, Dou Du, Yan Zhang, Yu Chen, Huixiong Xu. Ultrasound-
Controlled CRISPR/Cas9 System Augments Sonodynamic Therapy of
Hepatocellular Carcinoma. ACS Central Science, 2021; DOI: 10.1021/
acscentsci.1c01143 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211208085956.htm

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