Platform Vector Gene Therapy (PaVe-GT) Pilot Project

New technologies — including using viruses to move properly working genes to cells that need them — are making gene therapy more appealing to people with rare genetic diseases. Yet, due to the high costs of therapy development and low return on investment, many companies may not want to spend the time and money it takes to develop, test and bring to market gene therapy for a very rare disease.

NCATS, along with NIH’s National Human Genome Research Institute and National Institute of Neurological Disorders and Stroke, began the PaVe-GT pilot project in 2019 to test the hypothesis of whether a platform vector approach will increase efficiency in preclinical testing and clinical trial start-up.

The goal of the PaVe-GT project is to test the outcome of using the same gene delivery system and manufacturing methods in several rare disease gene therapy clinical trials. More specifically, PaVe-GT researchers are using a common gene delivery vehicle, adeno-associated virus (AAV), to create gene therapies for four rare genetic diseases. Each disease is being currently studied at the NIH Clinical Center. They include two inherited muscle weakness/neuromuscular junction disorders (Dok7 deficiency and Collagen Q deficiency) and two inherited metabolic diseases (propionic acidemia and isolated methylmalonic acidemia).

By including many diseases at a time, the PaVe-GT team is working to improve the efficiency of the clinical trial startup process for gene therapy and develop a standardized “blueprint” for similar gene therapy projects focused on rare diseases. To allow others to benefit and learn from the process taken in PaVe-GT, the team publicly shares the scientific and regulatory experience while applying this approach. This includes lessons learned from preclinical toxicology and biodistribution studies, manufacturing processes and regulatory documentation, including Investigational New Drug filings, communications with the U.S. Food and Drug Administration (FDA) and other proprietary documents, on the PaVe-GT website.