New Cellular Pathway Discovered to Enhance Gene Therapy Safety

Researchers at the Centenary Institute and the University of Sydney have unveiled a significant breakthrough in gene therapy, potentially transforming treatment for serious genetic disorders such as Duchenne muscular dystrophy, Pompe disease, and hemophilia. Published on July 15, 2025, in the prestigious journal *Cell*, the study identifies a novel receptor known as AAVR2 that facilitates the entry of therapeutic viruses into human cells, offering a new strategy to enhance the safety and efficacy of gene therapies.

This groundbreaking discovery suggests that by utilizing AAVR2, medical professionals may be able to administer lower doses of adeno-associated viruses (AAVs), which are commonly used in gene therapies. According to Dr. Bijay Dhungel, lead author of the study and researcher at the Centenary Institute’s Centre for Rare Diseases and Gene Therapy, this alternative entry route could mitigate adverse immune reactions and reduce treatment costs, thereby improving patient outcomes. “We found that certain AAV types can use this newly identified receptor, AAVR2, to enter cells, providing an alternative to the previously known entry route,” Dr. Dhungel remarked.

Gene therapies, which involve the use of modified viruses to deliver healthy genes into patients, have shown immense potential in treating a variety of genetic disorders. However, current methodologies frequently necessitate high vector doses that can provoke severe immune responses, sometimes resulting in serious complications or even fatalities. Thus, the ability to exploit AAVR2 to enhance cellular entry represents a pivotal advancement in the field.

Co-senior author Dr. Charles (Chuck) Bailey, Head of the Centre for Rare Diseases and Gene Therapy at the Centenary Institute, emphasized the implications of this research, stating, “We not only identified this new receptor AAVR2 but also discovered how it binds to the viruses that deliver the genes. We then engineered a miniature version of the receptor, which significantly enhances the efficiency of gene therapy uptake in human cells and tissues.”

The findings of this study are expected to reshape the landscape of gene therapy, as they provide novel strategies to tailor treatments and potentially avoid immune-related complications that have hindered current approaches. This research was supported by funding from several organizations, including NSW Health, the National Health and Medical Research Council (NHMRC), and Therapeutic Innovation Australia, highlighting its scientific and clinical significance.

In summary, the identification of AAVR2 as a critical receptor for gene therapy delivery marks a promising advancement in the quest for safer, more effective therapeutic strategies for genetic disorders. This discovery not only enhances scientific understanding of viral interactions with human cells but also paves the way for the development of precision-guided gene therapies that may soon improve accessibility and outcomes for patients worldwide.