Cell-penetrating peptides (CPPs), which may be readily conjugated to charge neutral AOs such as PMO, have shown potential for improved systemic delivery. CPPs that contain cationic amino acids, particularly multiple arginines, are highly effective in enhancing AO delivery due to their unique ability to deliver associated cargoes across the plasma and endosomal membranes. 20 Various arginine-rich peptides have been found to be particularly effective for delivery of such charge neutral AOs, [21] [22] [23] leading to systemic dystrophin production. However, dystrophin protein restoration in heart has typically required repeated 24 and/or very high dose administrations. 25