03121: Optimizing HITI CRISPR/Cas9 Gene Editing for Treating Defective Pyruvate Dehydrogenase Kinase 4 in Doberman Pinschers

One Health: Yes

Abstract

Approximately 10% of all dogs in the United States have some form of heart disease which can progress to heart failure. Novel therapeutic strategies are urgently needed to treat the disease. Doberman Pinschers affected by a specific form of dilated cardiomyopathy (or DCM) have a high mortality rate, with mean survival times less than 6 months following the first episode of congestive heart failure.

Dilated Cardiomyopathy in canines has been linked to two major genetic defects, including one gene called pyruvate dehydrogenase kinase 4 (PDK4). This metabolic gene is missing a DNA sequence that is required for optimal functioning of the heart. New approaches in gene editing show promise for treating cardiomyopathies. This project will use a technique called homology-independent target integration (HITI) to insert a corrected sequence into the homozygous cells with the mutation, restoring damaged cells to normal capacity. The overarching goal of this collaborative project is to use gene editing to modify the PDK4 gene in Doberman Pinchers, resulting in healthy heart cells. These genetic studies have broader implications for many other susceptible breeds that have increased risk of heart disease.

Publication(s)

None at this time.