Washington University Researchers readily acknowledge the attributes of sonodynamic therapy (SDT) as a promising therapeutic method to treat hepatocellular carcinoma (HCC).

 SDT is noninvasive with high tissue penetration, but the cancer’s defense system is still able to restrict SDT. In addition, the researchers identified a molecule called NFE2L2  which contains oxygen. An accumulation of oxygen in cells can damage RNA, DNA, and proteins possibly cause cell death (apoptosis). The researchers noted that its activation in SDT inhibits SDT’s effectiveness.

The Solution

To prevent interference with SDT’s efficacy, the researchers constructed a CRISPR Cas9 release system that counters the adverse effects of NFE2L2 and increases the efficiency of SDT.

 Sufficient Reactive Oxygen Species (ROS) were generated by hematoporphyrin monomethyl ether (HMME) that damaged cancer cells while under ultrasound irradiation. ROS are small molecules that are highly reactive but short-lived.

The ROS that was generated brought about lysosomal rupture that released Cas9 RNA/RNP thus destroying the oxidative defense system and promoting tumor cell death.

About Hepatocellular Carcinoma (HCC).

Hepatocellular carcinoma is a primary liver cancer that starts in the liver. Although it is the sixth most common type of cancer in the world, it is the third leading cause of cancer deaths. The disease most commonly occurs in individuals who have had liver disease for years. 

 Looking Forward

The study has shown the value of CRISPR/Cas9 in HCC management while also demonstrating the successful combination of SDT together with gene editing.

Check out the full text of this study here in the journal ACS Central Science.