Delivery and evaluation of recombinant adeno-associated viral vectors in the equine distal extremity for the treatment of laminitis.
Authors: Mason J B, Gurda B L, Van Wettere A, Engiles J B, Wilson J M, Richardson D W
Journal: Equine veterinary journal
Summary
# Editorial Summary Researchers at the University of Pennsylvania investigated whether gene therapy vectors could be delivered effectively to deep structures within the equine foot via regional limb perfusion, with the ultimate goal of preventing laminitis in the contralateral limb of horses with severe lameness. Using three different recombinant adeno-associated viral (rAAV) serotypes—2/1, 2/8 and 2/9—administered through the palmar digital artery, the team assessed transduction efficiency across various foot tissues in a randomised in vivo trial. All three serotypes successfully transduced equine foot tissues with comparable efficacy, though distribution patterns varied; the sole and coronary band showed the highest transduction rates, whilst the dorsal hoof wall remained the most challenging target (achieving only 9–81-fold lower rates with saline alone). Critically, when vectors were suspended in surfactant-enriched rather than standard saline, transduction of the hoof wall increased dramatically—by 9- to 81-fold—significantly improving overall tissue distribution. For equine practitioners, these findings demonstrate that gene therapy delivery to the foot is technically feasible and that formulation adjustments can overcome anatomical barriers; whilst clinical applications for laminitis prevention remain investigational, this work establishes the foundation for developing disease-modifying therapies delivered directly to at-risk tissues.
Read the full abstract on PubMed
Practical Takeaways
- •Gene therapy delivery to the equine foot is feasible using rAAV vectors via regional limb perfusion, opening new preventive treatment options for contralateral laminitis
- •Formulation of the vector delivery medium (surfactant vs. saline) significantly impacts distribution and transduction efficiency in different foot regions, particularly the hoof wall
- •This approach may eventually allow therapeutic protein delivery directly to target tissues in the distal extremity without systemic drug administration
Key Findings
- •rAAV serotypes 2/1, 2/8, and 2/9 successfully transduced equine foot tissues with similar transduction levels and patterns
- •Sole and coronary regions showed highest transduction; dorsal hoof-wall showed lowest transduction
- •Surfactant-enriched vector diluent increased hoof-wall transduction 9- to 81-fold compared to saline alone
- •Vector dose correlated with regional distribution of transduction throughout foot tissues