In vivo gene therapy of the equine distal extremity with recombinant adeno-associated viral vectors

Equine laminitis is a crippling disease that affects all breeds of horses and is commonly a career-ending and often life-threatening disease. Treatment of laminitis continues to be a controversial topic in equine veterinary medicine because there is a lack of universally efficacious treatment modalities. We recently developed a practical method to efficiently deliver transgene-produced proteins deep within the equine foot. We used recombinant adeno-associated viral vectors (rAAVs) to deliver marker genes through the palmar digital artery. Vector serotypes rAAV2/1, 2/8 and 2/9 all successfully transduced tissues deep within the enclosed confines of the keratinized hoof-wall without disrupting the native architecture of the foot and all displayed similar levels and patterns of transduction. The use of a surfactant-enriched vector diluent increased regional distribution of the vector and improved the transduction in the hoof-wall region. However, all horses that were tested for vector-neutralizing antibodies were positive for serotype-specific neutralizing antibodies to rAAV2/5. This is the first time an rAAV has been successfully used to transduce tissues of the equine distal extremity and provides a positive outlook for the future therapeutic potential of gene therapy in the equine foot.