Researchers at Oregon Health & Science University have achieved a groundbreaking milestone in hepatitis B virus research by developing the first transgenic nonhuman primate model genetically modified to carry a human gene. This innovative model opens up new possibilities for studying the virus and potentially developing novel treatments for the disease, which impacts millions of people worldwide and causes significant mortality rates.
The study, published in the Proceedings of the National Academy of Sciences, was led by Ben Burwitz, Ph.D., an associate professor at OHSU’s Oregon National Primate Research Center. Hepatitis B virus (HBV) primarily infects humans and a few other non-rodent species, posing challenges in creating animal models that accurately replicate the human immune response to the virus. Current nonhuman primate models involve temporary modifications, such as introducing the human HBV entry receptor NTCP into liver cells using viral vectors. However, these methods are not very efficient and can be short-lived due to immune system interference.
The breakthrough achieved by Burwitz’s team involved inserting NTCP directly into the genetic material of rhesus macaques, making them naturally susceptible to HBV infection. This was made possible through the use of the Piggybac gene-editing system, which, although less precise than CRISPR, proved to be highly efficient in this context. The researchers successfully edited the genes of seven nonhuman primates, identifying two individuals that carried the transgene. Importantly, the transgene was expressed only in the liver, a crucial factor for future HBV infection studies.
The implications of this research are immense, as the transgenic nonhuman primate model closely mimics the human liver-specific susceptibility to HBV. This paves the way for studying chronic HBV infections and testing potential treatments in a more accurate and efficient manner than ever before. Chronic HBV infections are particularly concerning, as they can lead to severe complications such as liver cancer. By utilizing this model, researchers can explore new therapeutic approaches, including small-molecule drugs that could potentially offer a cure for the disease.
Beyond HBV research, the team’s gene-editing technologies have broader applications for studying various diseases that affect human organs. The flexibility of the system allows for easy modifications to study other diseases specific to certain organs, opening up possibilities for investigating co-infections and comorbidities. This new model represents a significant step forward in the field of viral research and holds promise for advancing our understanding of complex diseases and developing effective treatments.
The work conducted by Burwitz and his team showcases the power of genetic engineering in biomedical research and highlights the potential for using transgenic animal models to address critical health challenges. As they continue to refine and expand their model, the hope is to accelerate the development of new therapeutics for HBV and other viral diseases, ultimately improving outcomes for patients worldwide.
