Development of a Novel AAV Vector Capsid Optimized for OA Gene Therapy
Abstract
Osteoarthritis (OA) is a chronic, degenerative, often crippling disease that primarily affects large weight-bearing joints. OA is most commonly linked to wear and tear of the joints from old age. In younger people, though, it arises from a significant joint injury, one that damages the bones and cartilage (post-traumatic osteoarthritis; PTOA). Indeed, OA one of the primary causes of disability among active duty soldiers and veterans. Despite the constant claims in the media, there is no drug or dietary supplement capable of slowing joint destruction in OA and although some drugs can ease OA joint pain, they can't stop the erosive biological processes. We have been working to develop a gene-based therapy for OA. Using a harmless virus, we can deliver the genes for these naturally-occurring anti-arthritic proteins to the cells and tissues in diseased joints. Following a single injection, the diseased joints continually make their own medicine for well over a year. This experimental treatment has worked exceptionally well, first in small animals and then in the joints of horses similar in size to human knees that are also highly prone to OA. Following detailed toxicology studies this treatment was approved by the FDA for safety testing in humans with knee OA. In the current project we will use a highly advanced, state-of-the-art system developed by a member of our research team, to develop a new, custom-made AAV vector, optimized specifically for use in gene therapy for human OA. This system has been used to generate vectors with dramatically enhanced potency in treatments for blindness, cancer and liver disease. Based the successes in these applications, we expect to generate a delivery system for human OA 10-100x more effective than our current version. This new vector will be invisible to childhood antibodies, easier to manufacture and most importantly will be safe for use in humans with joint disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2021
- Accession Number
- AD1152688
Entities
People
- Sergei Zolotukhin
- Steven C. Ghivizzani
Organizations
- University of Florida