Strategies and Challenges for Non-Viral Delivery of Non-Coding RNAs to the Heart

Non‐coding RNAs (ncRNAs), such as miRNAs and long non‐coding RNAs (lncRNAs) have been reported as regulators of cardiovascular pathophysiology. Their transient effect and diversified mechanisms of action offer a plethora of therapeutic opportunities for cardiovascular diseases (CVDs). However, physicochemical RNA features such as charge, stability, and structural organization hinder efficient on-target cellular delivery. Here, we highlight recent preclinical advances in ncRNA delivery for the cardiovascular system using non‐viral approaches. We identify the unmet needs and advance possible solutions towards clinical translation. Finding the optimal delivery vehicle and administration route is vital to improve therapeutic efficacy and safety; however, given the different types of ncRNAs, this may ultimately not be frameable within a one-size-fits-all approach.