Navigating the prime editing strategy to treat cardiovascular genetic disorders in transforming heart health.

ABSTRACT

INTRODUCTION: After understanding the genetic basis of cardiovascular disorders, the discovery of prime editing (PE), has opened new horizons for finding their cures. PE strategy is the most versatile editing tool to change cardiac genetic background for therapeutic interventions. The optimization of elements, prediction of efficiency, and discovery of the involved genes regulating the process have not been completed. The large size of the cargo and multi-elementary structure makes the in vivo heart delivery challenging. AREAS COVERED Updated from recent published studies, the fundamentals of the PEs, their application in cardiology, potentials, shortcomings, and the future perspectives for the treatment of cardiac-related genetic disorders will be discussed. EXPERT OPINION The ideal PE for the heart should be tissue-specific, regulatable, less immunogenic, high transducing, and safe. However, low efficiency, sup-optimal PE architecture, the large size of required elements, the unclear role of transcriptomics on the process, unpredictable off-target effects, and its context-dependency are subjects that need to be considered. It is also of great importance to see how beneficial or detrimental cell cycle or epigenomic modifier is to bring changes into cardiac cells. The PE delivery is challenging due to the size, multi-component properties of the editors and liver sink.