Transgenic Primate Model Revolutionizes HBV Research

On February 13, 2025, researchers from Oregon Health & Science University (OHSU) announced a significant breakthrough in hepatitis B research with the development of the first transgenic nonhuman primate model. This model is genetically modified to express a human gene, thereby paving the way for more effective studies of the hepatitis B virus (HBV), a disease that afflicts approximately 250 million individuals worldwide and contributes to nearly 1 million deaths each year.

The Challenge of Hepatitis B Research

Hepatitis B virus uniquely affects humans and a limited number of non-rodent species, complicating the creation of adequate animal models for research. Previous attempts to use nonhuman primates typically involved temporary modifications that added the HBV entry receptor, a human protein known as NTCP, to liver cells via viral vectors. However, these methods often demonstrated low efficiency, temporary effects, and susceptibility to immune system interference.

Dr. Ben Burwitz, an associate professor at OHSU’s Oregon National Primate Research Center, emphasized the groundbreaking nature of this research, stating that the newly developed model “mimics human liver-specific susceptibility to HBV.”

Creation of the Transgenic Primate Model

The researchers employed a gene-editing technique called Piggybac, which, while less precise than CRISPR, proved to be significantly more efficient—especially crucial when dealing with embryos in >IVF procedures. The team successfully edited the genes of seven rhesus macaques, achieving the insertion of NTCP into their genetic material.

“This means the nonhuman primates can be infected with HBV in lab tests without any additional modifications. It's a huge step forward.” – Lauren Rust, Ph.D., Lead Author

Implications of the Research

The presence of the transgene was confirmed across various tissues, with expression limited to the liver, which is vital for accurate HBV infection studies. The next phase will involve breeding these primates to observe the development of chronic HBV infections when exposed to the virus at birth—a reflection of the virus's natural progression in human cases.

Hepatitis B remains a formidable public health challenge. It transmits primarily through contact with infected blood or bodily fluids, with chronic cases often originating from mother-to-child transmission at birth. Dr. Rust highlighted a grim fact: “Most babies infected at birth develop chronic infections, which can lead to complications such as liver cancer.”

Future Research Directions

The aim is to utilize this new model to investigate chronic HBV and evaluate potential treatment approaches. The findings could be instrumental in developing small-molecule drugs in pill form that could offer a cure, an area that has seen limited success in HBV management.

Dr. Burwitz remarked on the research's broader implications, stating that while progress has been made in immunotherapies for HBV, many existing treatments are costly and logistic-intensive, necessitating stable temperature conditions for transport. The ongoing research from Burwitz's lab will prioritize making such treatments more accessible and effective.

Broader Applications of the Transgenic Model

The applicability of this model extends beyond hepatitis B. As researchers refine their gene-editing technologies, they anticipate creating transgenic models for various diseases affecting human organs. This adaptability opens avenues for exploring co-infections and comorbidities, particularly the interplay between HBV and HIV, which complicates patient outcomes.

The research conducted at OHSU represents not only a leap in our understanding of HBV but also a promising foundation for future studies addressing various diseases. This transgenic primate model could significantly enhance our ability to test treatments and understand chronic infections in ways previously unattainable.

Further Reading

For more in-depth information on this topic, you can access the original article published in the Proceedings of the National Academy of Sciences.

Reference: Rust, L. N., et al. (2025). Liver-specific transgenic expression of human NTCP in rhesus macaques confers HBV susceptibility on primary hepatocytes. Proceedings of the National Academy of Sciences.

Conclusion

This pioneering work not only sheds light on the mechanisms of hepatitis B infection but also heralds new beginnings for treatment strategies that could improve the lives of many affected individuals worldwide.