Department of Bioengineering, College of Engineering, Hanyang University, Wangsimni-ro 222, Seongdong-gu, Seoul 04763, Republic of Korea.
Department of Bioengineering, College of Engineering, Hanyang University, Wangsimni-ro 222, Seongdong-gu, Seoul 04763, Republic of Korea.
J Control Release. 2023 Aug;360:1-14. doi: 10.1016/j.jconrel.2023.06.018. Epub 2023 Jun 19.
Acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) is a devastating inflammatory lung disease with a high mortality rate. ALI/ARDS is induced by various causes, including sepsis, infections, thoracic trauma, and inhalation of toxic reagents. Corona virus infection disease-19 (COVID-19) is also a major cause of ALI/ARDS. ALI/ARDS is characterized by inflammatory injury and increased vascular permeability, resulting in lung edema and hypoxemia. Currently available treatments for ALI/ARDS are limited, but do include mechanical ventilation for gas exchange and treatments supportive of reduction of severe symptoms. Anti-inflammatory drugs such as corticosteroids have been suggested, but their clinical effects are controversial with possible side-effects. Therefore, novel treatment modalities have been developed for ALI/ARDS, including therapeutic nucleic acids. Two classes of therapeutic nucleic acids are in use. The first constitutes knock-in genes for encoding therapeutic proteins such as heme oxygenase-1 (HO-1) and adiponectin (APN) at the site of disease. The other is oligonucleotides such as small interfering RNAs and antisense oligonucleotides for knock-down expression of target genes. Carriers have been developed for efficient delivery for therapeutic nucleic acids into the lungs based on the characteristics of the nucleic acids, administration routes, and targeting cells. In this review, ALI/ARDS gene therapy is discussed mainly in terms of delivery systems. The pathophysiology of ALI/ARDS, therapeutic genes, and their delivery strategies are presented for development of ALI/ARDS gene therapy. The current progress suggests that selected and appropriate delivery systems of therapeutic nucleic acids into the lungs may be useful for the treatment of ALI/ARDS.
急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）是一种具有高死亡率的破坏性炎症性肺部疾病。ALI/ARDS 由多种原因引起，包括败血症、感染、胸部创伤和吸入有毒试剂。新型冠状病毒肺炎（COVID-19）也是 ALI/ARDS 的主要病因。ALI/ARDS 的特征是炎症损伤和血管通透性增加，导致肺水肿和低氧血症。目前治疗 ALI/ARDS 的方法有限，但包括机械通气以进行气体交换和支持减少严重症状的治疗。已经提出了抗炎药物，如皮质类固醇，但它们的临床效果存在争议，可能有副作用。因此，已经为 ALI/ARDS 开发了新的治疗方法，包括治疗性核酸。有两类治疗性核酸在使用。第一类是在疾病部位插入编码治疗性蛋白的基因，如血红素加氧酶-1（HO-1）和脂联素（APN）。另一种是寡核苷酸，如小干扰 RNA 和反义寡核苷酸，用于敲低靶基因的表达。根据核酸的特性、给药途径和靶向细胞，已经开发了用于高效递送至肺部的治疗性核酸的载体。在这篇综述中，主要讨论了基于载体的 ALI/ARDS 基因治疗。介绍了 ALI/ARDS 的病理生理学、治疗基因及其传递策略，为 ALI/ARDS 基因治疗的发展提供了依据。目前的进展表明，将治疗性核酸选择性和适当地递送至肺部可能对治疗 ALI/ARDS 有用。
