Platform Vector Gene Therapy (PaVe-GT) Pilot Project

This NIH initiative led by NCATS aims to make gene therapy development and clinical testing more streamlined, more efficient, and potentially more accessible to many people with rare diseases.

New technologies — including the use of viruses to deliver genes to cells that need properly functioning genes — are making gene therapy an increasingly attractive treatment option for individuals with rare genetic diseases. Yet, thousands of these disorders are so rare that companies might be reluctant or unable to invest the years of research and the millions of dollars needed to develop, test and bring a gene therapy for a very rare disease to market.

To address the unmet need for more efficient gene therapy clinical development, NCATS, along with NIH’s National Human Genome Research Institute, National Institute of Neurological Disorders and Stroke, and Eunice Kennedy Shriver National Institute of Child Health and Human Development, launched the Platform Vector Gene Therapy (PaVe-GT) pilot project in February 2019. The goal of this project is to test the impact of using the same gene delivery system and manufacturing methods in multiple rare disease gene therapy clinical trials.

Watch this video to meet the investigators behind PaVe-GT. The video aired during Rare Disease Day at NIH, which was held virtually on March 1, 2021.

A version of this video with audio description is available.

More specifically, PaVe-GT researchers will use a common gene delivery vehicle, adeno-associated virus (AAV), to create gene therapies for four rare genetic diseases. Each disease currently is being 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). Researchers plan to use the same manufacturing process and AAV delivery system to carry a therapeutic gene to the right place in the body for all four diseases, but simply switch the cargo — the gene — for each disease.

In this many-diseases-at-a-time approach, 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 enable others to benefit and learn from the scientific and procedural path taken in PaVe-GT, the PaVe-GT team will make preclinical toxicology and biodistribution data, Investigational New Drug filings, communications with the U.S. Food and Drug Administration (FDA), and other study documents normally considered proprietary by companies available to the public on the PaVe-GT website.

Read the original press release on PaVe-GT: Collaborative NIH Effort Aimed at Creating a Gene Therapy Playbook, Making Rare Disease Treatments More Accessible.

To hear more about PaVe-GT, watch former NCATS' Office of Rare Diseases Research Director Anne Pariser's I Am Translational Science video.

Hear from PaVe-GT scientists about their successful applications for an Orphan Drug Designation and a Rare Pediatric Disease designation from FDA.

For more information, please contact P.J. Brooks, Ph.D.