931. Enhanced Cardiac Muscle Contractility Achieved by Engineered Zinc Finger Transcriptional Repressors of Phospholamban

Phospholamban (PLN) is a critical regulator of cardiac calcium homeostasis and muscle contractility. Recent studies have demonstrated that ablation or inhibition of PLN function can improve cardiac contractile properties in animal models of congestive heart failure (CHF), suggesting that PLN is an attractive target for treatment of CHF. Because of its use of a large, relatively flat interaction surface when docking with its regulation target (Sarcoplasmic Reticulum Ca2+ ATPase 2 isoform A (SERCA2a)), the development of small-molecule inhibitors of PLN function is expected to be extremely challenging. Therefore, approaches that aim to block the expression of PLN may provide a superior means of achieving the desired therapeutic effect.