MicroRNA-Based Therapeutic Strategies for Pulmonary ArterialHypertension under Different Delivery Systems: Progress andChallenges

Introduction: Pulmonary arterial hypertension (PAH) is a serious disease with high morbidity and mortality, and current treatments fail to significantly improve prognosis, necessitating the exploration of new therapeutic targets. MicroRNAs (miRNAs), as key post-transcriptional regulators, are emerging as potential therapeutic targets for PAH. Due to microRNA's susceptibility to degradation, the choice of delivery method is critical for microRNA therapy in pulmonary hypertension. Methods: We provide a detailed introduction and comparison of pharmacological methods for regulating miRNAs, including enhancing the stability of nucleoside analogues, viral vectors, non-viral vectors, and combinations of viral and non-viral vectors. Results: Our analysis identifies that while each delivery modality can effectively modulate specific miRNA pathways and influence PAH progression in preclinical models, hybrid delivery systems demonstrate superior potential by balancing delivery efficiency with safety profiles. Discussion: Despite promising preclinical findings, substantial challenges remain regarding biosafety, long-term efficacy, and translational feasibility. Optimization of miRNA stability and delivery specificity is essential for future clinical applications. Conclusion: Currently in the early stages of research, there are significant challenges to the safety and efficacy of applications targeting microRNAs, but advances in these strategies may lead PAH therapy into a new era of personalized, precision medicine.