An Opisthorchis viverrini worm. Image credit: Sripa et al. (2007) Liver Fluke Induces Cholangiocarcinoma. PLoS Medicine (CC BY 2.5)
In the rural regions alongside the Mekong River in South East Asia, traditional cuisines often use uncooked or under cooked fish, many of which carry a worm known as Opisthorchis viverrini. Once inside the body, this parasite settles in the human liver, causing a tropical disease known as liver fluke infection. Out of the 10 million people affected by O. viverrini, thousands will also develop a type of liver cancer that is triggered by the presence of the worm. In particular, the parasite secretes a protein known as granulin that may encourage certain liver cells to multiply, potentially raising the risk for cancer.
A gene editing technique called CRISPR/Cas9 allows scientist to precisely target and then deactivate the genetic information a cell needs to produce a given protein. While the tool has been used in other species before, it was unknown if it could be applied to O. viverrini. Here, Arunsan et al. harnessed CRISPR/Cas9 to deactivate the gene that codes for granulin and create parasites that can only produce very little of the protein.
Hamsters infected with the gene-edited worms had fewer symptoms of liver fluke infection compared to those carrying normal O. viverrini. The animals with parasites that cannot produce granulin also had fewer changes to the liver that are associated with cancer. These findings confirm that granulin has a role in promoting liver fluke infection and liver cancer.
Alongside this work, Ittiprasert et al. used CRISPR/Cas9 to inactivate a gene in a species of worm that causes a human disease called schistosomiasis. Together, these findings demonstrate for the first time that the gene editing method can be adapted for use in parasitic worms, which are a major public health problem in tropical climates. This tool should help scientists understand how the parasites invade and damage our bodies, and provide new ideas for treatment and disease control.
