Gene Therapy Enhancers
The development of gene therapy began roughly 50 years ago and has recently gained FDA approval for an increasing number of diseases. This approach works by using a delivery vehicle to transport a functional copy of a gene into cells that carry a disease-causing mutation. Such mutations typically result in a missing or dysfunctional protein; once delivered, the healthy gene enables the cell’s own machinery to produce the correct protein, thereby alleviating patient symptoms.
Common delivery vehicles include viral vectors, polymeric nanoparticles, and lipid nanoparticles. While our lab investigates a range of these platforms, we have focused primarily on the viral vector adeno-associated virus (AAV). To enhance AAV's performance, we engineered a class of helper nanoparticles we call "ePL." When co-administered with AAV, these nanoparticles improve tissue targeting and reduce the vector's immunogenicity.
ePL was tested in both mice and non-human primates and showed excellent safety. ePL enabled a more than 10-fold reduction in the effective AAV dose while maintaining comparable therapeutic targeting. This dose reduction is critically important, as AAV-based drugs are among the most expensive biologics to manufacture, which significantly drives up costs for patients and healthcare systems. Additionally, we observed that ePL diminishes neutralizing antibodies – a major driver of immune responses against viral vectors. These findings open the door to discovering even more potent ePL-like nanoparticles, with the potential to one day transform gene therapy into a safer, more effective, and broadly accessible treatment.
