In a groundbreaking study published in the journal Nature Communications, scientists from Children’s Medical Research Institute (CMRI) have conducted the first-ever gene therapy tests in a whole human liver. This pioneering research aims to develop more effective treatments for life-threatening inherited diseases.
Gene therapy is a revolutionary approach to treating serious genetic diseases, typically involving the replacement or repair of a faulty gene. The most efficient delivery systems currently rely on the adeno-associated virus (AAV), a harmless virus with the natural ability to carry genetic information into human cells.
One of the major challenges in bringing gene therapies from the lab to the clinic is the lack of effective preclinical models for developing and testing new therapies. Researchers require biologically relevant and clinically predictive laboratory tests to accurately predict the outcomes when administering the therapy to patients. The ability to reproduce human physiological conditions and tissue organization in these models is crucial.
Last year, CMRI’s Translational Vectorology Research Unit collaborated with a team at Royal Prince Alfred Hospital to develop a method for keeping a human liver alive in a lab setting. This innovative normothermic liver perfusion system enables the preservation of livers unsuitable for transplantation at human body temperature, allowing for cutting-edge biomedical research.
Building on this achievement, the CMRI team has demonstrated the potential of using this system to test AAV-based therapeutics before initiating clinical studies. The utilization of the whole human liver represents a significant advancement in gene therapy, enabling researchers to accurately assess the impact of new therapeutics on a major organ, the liver, which was previously unattainable.
Associate Professor Leszek Lisowski, the senior author of the publication, expressed excitement about the groundbreaking potential of directly assessing the function of gene therapeutics in the human liver. This development is particularly significant given the current limitations of viral vectors used for delivering gene therapeutics to the liver.
