Title of Oral/Poster Presentation

Employing Recombinant Adeno-associated Viral Vectors for Delivery of a Therapeutic Timp-3 Transgene to the Equine Distal Extremity Using a Clinical Regional Limb Perfusion Technique.

Class

Article

College

College of Agriculture and Applied Sciences

Faculty Mentor

Jeff Mason

Presentation Type

Poster Presentation

Abstract

Equine laminitis is a condition that results in lameness, extreme pain, long-term care and in many cases, concludes in euthanasia. Because of the nature of equine hoof structure, current treatment options are limited and supportive care is the only possibility. However, gene therapy has manifested promising results for preventing laminitis. The epidermal and dermal layers of the hoof are stabilized by connective tissues partly composed of proteoglycans known as aggrecans. The Tissue Inhibitor of Metalloproteinase-3 (Timp-3) is an extracellular protein that inhibits aggrecanase-mediated aggrecan degradation. Previous studies in our lab have shown that recombinant adeno-associated viral vectors (rAAVs) can be administered using a common, clinical standing regional limb perfusion (RLP) procedure and have resulted in the transduction of marker genes (LacZ) deep within the lamellar tissues of the distal extremity. The current study will use rAAVs containing a therapeutic, codon optimized Timp-3 transgene. Hoof tissue samples will be harvested for analysis 28 days post-injection. We expect to find that the tissues of the foot are transduced with the therapeutic Timp-3 gene and that the Timp-3 protein has been produced endogenously by transfected cells. Favorable results will allow for future clinical studies which evaluate the effects of gene therapy on equine laminitis.

Location

The South Atrium

Start Date

4-12-2018 12:00 PM

End Date

4-12-2018 1:15 PM

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Apr 12th, 12:00 PM Apr 12th, 1:15 PM

Employing Recombinant Adeno-associated Viral Vectors for Delivery of a Therapeutic Timp-3 Transgene to the Equine Distal Extremity Using a Clinical Regional Limb Perfusion Technique.

The South Atrium

Equine laminitis is a condition that results in lameness, extreme pain, long-term care and in many cases, concludes in euthanasia. Because of the nature of equine hoof structure, current treatment options are limited and supportive care is the only possibility. However, gene therapy has manifested promising results for preventing laminitis. The epidermal and dermal layers of the hoof are stabilized by connective tissues partly composed of proteoglycans known as aggrecans. The Tissue Inhibitor of Metalloproteinase-3 (Timp-3) is an extracellular protein that inhibits aggrecanase-mediated aggrecan degradation. Previous studies in our lab have shown that recombinant adeno-associated viral vectors (rAAVs) can be administered using a common, clinical standing regional limb perfusion (RLP) procedure and have resulted in the transduction of marker genes (LacZ) deep within the lamellar tissues of the distal extremity. The current study will use rAAVs containing a therapeutic, codon optimized Timp-3 transgene. Hoof tissue samples will be harvested for analysis 28 days post-injection. We expect to find that the tissues of the foot are transduced with the therapeutic Timp-3 gene and that the Timp-3 protein has been produced endogenously by transfected cells. Favorable results will allow for future clinical studies which evaluate the effects of gene therapy on equine laminitis.