Gene-Editing Tool CRISPR/Cas9 Shown to Limit Impact of Certain Parasitic Diseases

GW researchers successfully used CRISPR/Cas9 to limit the impact of schistosomiasis and liver fluke infection, affecting more than a quarter of a billion people in Southeast Asia, sub-Saharan Africa, and Latin America
Dr. Paul Brindley posing for a portrait

WASHINGTON (Jan. 15, 2019) — For the first time, researchers at the George Washington University (GW), together with colleagues at institutes in Thailand, Australia, the U.K. and the Netherlands, and more, have successfully used the gene-editing tool CRISPR/Cas9 to limit the impact of parasitic worms responsible for schistosomiasis and for liver fluke infection, which can cause a diverse spectrum of human disease including bile duct cancer. Their findings are found in two papers published today in the journal eLife.

“The genes we ‘knocked out’ using CRISPR/Cas9 resulted in markedly diminished symptoms of infection in our animal models,” said Paul Brindley, PhD, professor of microbiology, immunology, and tropical medicine at the GW School of Medicine and Health Sciences, and lead author. “Our research also showed that this revolutionary new biomedical procedure — CRISPR/Cas9 — can be adapted to study helminth parasites, which are a major public health problem in tropical climates.”

CRISPR/Cas9 is a new technology that allows researchers to precisely target and deactivate the genetic information needed to produce a particular protein. While the tool has been used in other species before, it was unknown if it could be applied to Schistosoma mansoni and Opisthorchis viverrini, the parasites responsible for schistosomiasis and liver fluke infection.

Schistosomiasis can cause serious health problems, including damage to the liver and kidneys, infertility and bladder cancer. The freshwater worms S. mansoni enter the human body by burrowing into the skin; once in the bloodstream, they move to various organs where they rapidly start to reproduce. Their eggs release several molecules, including a protein known as omega-1 ribonuclease, which can damage the surrounding tissues. Brindley and his research team “knocked out” this protein using CRISPR/Cas9 and found that it greatly reduced the impact of the disease. 

Liver fluke infection can cause a type of liver cancer called bile duct cancer, triggered by the presence of the worm O. viverrini. This parasite is transmitted through traditional Southeast Asian cuisines using uncooked or undercooked fish. Once inside the body, the parasite settles in the human liver and secretes a protein known as granulin that may encourage liver cells to multiply, raising the risk for cancer. Brindley and his research team used CRISPR/Cas9 to deactivate the gene that codes for granulin and create parasites that can only produce very little of the protein, leading to markedly reduced symptoms of liver fluke infection. 

“These neglected tropical diseases affect more than a quarter of a billion people primarily living in Southeast Asia, sub-Saharan Africa, and Latin America,” said Brindley. “CRISPR/Cas9 is a tool that may be used to limit the impact of these infections. As we work to better understand how these parasites invade and damage our bodies through this new technology, we will find new ideas for treatment and disease control.”

Key collaborators include Karl Hoffmann, PhD at the Aberystwyth University, United Kingdom; Thewarach Laha, PhD at Khon Kaen University, Thailand; and Alex Loukas, PhD at James Cook University, Australia.

The papers, titled “Programmed genome editing of the omega-1 ribonuclease of the blood fluke, Schistosoma mansoni” and “Programmed knockout mutation of liver fluke granulin attenuates virulence of infection-induced hepatobiliary morbidity,” are available at eLife.

Latest News

The George Washington University School of Medicine and Health Sciences (GW SMHS) welcomed the MD Class of 2029 at the 27th Annual White Coat and Honor Code Ceremony, marking the first class of the school’s third century. The ceremony marked a public commitment to the profession and the beginning…
The Global Clinical Care Alliance (GCCA) at the George Washington University (GW) School of Medicine and Health Sciences (SMHS) announced the inaugural recipients of the GW Global Health Legacy Fellowship.
As fall begins and school resumes, the GW Cancer Center extends vital support to patients who are also parents. Led by Access Team Lead Janelle Williams, the center offers compassionate programs like school supply drives to ease the burden on families affected by cancer.