核酸药物在炎症性疾病领域的研究进展OA

When inflammation is continuously activated or dysregulated,it can induce chronic tissue injury and organ dysfunction,and participate in the occurrence and development of various inflammatory diseases such as atherosclerosis and inflammatory bowel disease.Owing to high targeting,long-acting efficacy and programmability,nucleic acid drugs provide a new direction for the treatment of inflammatory diseases.This article reviews the classification,mechanism of action and application progress of nucleic acid drugs in inflammatory diseases.It is found that small interfering RNA(siRNA)can specifically cut target mRNA through RNA interference to achieve inhibiting the expression of the target protein;antisense oligonucleotide(ASO)can inhibit target protein expression by inducing microRNA(miRNA)degradation or regulating splicing processes;miRNA can achieve network intervention by regulating multiple inflammatory target genes.At present,important breakthroughs have been made in the field of inflammatory diseases with siRNA drugs including Lumasiran,Nedosiran(for primary hyperoxaluria 1)and Inclisiran(for atherosclerosis),ASO drugs including Donidalorsen(for hereditary angioedema),Volanesorsen and Olezarsen(for familial chylomicronemia syndrome)and Lademirsen(for Alport syndrome),as well as miRNA drugs including Obefazimod(for inflammatory bowel disease)and Remlarsen(for pathological fibrosis).These drugs are expected to become a new generation of anti-inflammatory therapeutic strategies and bring more precise and efficient treatment options for patients with chronic inflammation and fibrotic diseases.