The May 2020 “VTPP Science in action” article comes from elegant studies from the laboratory of Dr. Charles Long, published in Scientific Reports. The studies were performed by a former MSc student Carlos Pinzon-Arteaga (now PhD student at UTSW). In this breakthrough work, Dr. Long’s team was able to use the CRISPR/Cas9 system to correct an autosomal recessive mutation responsible for Glycogen Branching Enzyme Deficiency (GBED). The disease is an inheritable glycogen storage disease that affects American Quarter Horses and American Paint Horses. Approximately 9% of all Quarter Horse and Paint Horse lineages are heterozygotic carriers of the mutation. GBED carriers have only 50% of the normal Glycogen Branching Enzyme activity and appear asymptomatic. The homozygous mutation is the cause of second and third-trimester abortion and significant foal mortality in the American Quarter Horse. The human form of the disease is called glycogen storage disease type IV. In the reported studies, the causal mutation (GBE1102C>A) was corrected in primary fibroblasts derived from an affected stallion. The next phase of the work will involve generation of a cloned animal that maintains the genetic merit of its predecessor and is free of the GBED mutation. In another important technical finding, the authors determined that the common misconception regarding numerous off-target effects of the CRISPR approach were not present. The studies have generated a new framework for efficient genome editing in primary equine fibroblasts and demonstrate that the proximity of the Cas9 enzyme cut site to the mutation site as well as the stability of the repair template are the primary factors affecting gene editing. Congratulations again to Dr. Long, Carlos and all the co-authors. The article (attached to this email) can be found at: https://www.nature.com/articles/s41598-020-62723-3
