烟台大学学报（自然科学与工程版）2026，Vol.39Issue(2)：151-159,9.DOI:10.13951/j.cnki.37-1213/n.241112
沉默CIDEB基因治疗非酒精性脂肪肝病的siRNA筛选与评价
SiRNA Screening and Evaluation of Silencing CIDEB Gene Therapy for Nonalcoholic Steatohepatitis
摘要
Abstract
This study aimed to develop small interfering RNA(siRNA)therapeutics targeting the cell death-indu-cing DNA fragmentation factor-like effector B(CIDEB),a key player in nonalcoholic steatohepatitis(NASH),to achieve long-term and safe protein inhibition.Different humanized siRNAs sequences were designed to target CI-DEB,and cell models were constructed by introducing humanized psiCHECK-CIDEB double luciferase reporter genes at the cellular level for preliminary in vitro activity screening.The selected siRNAs were chemically modified and further screened and optimized.Subsequently,the GalNAc-siRNA conjugate was chemically synthesized for the optimized siRNA,and a CIDEB transgenic animal model was constructed for in vivo activity evaluation to identify candidate sequences with a significant silencing effect on CIDEB messenger RNA(mRNA).Three dose gradients(10,30,and 50 mg/kg)were used for the early in vivo safety evaluation of the optimal sequence.In vivo activity experiments showed that the optimized siRNA could significantly and long-term inhibit CIDEB expression in trans-genic mice(with a relative inhibition rate>80%for 4 weeks).A preliminary safety evaluation was conducted based on serum levels of glutamic oxalic aminotransferase,glutamic pyruvic aminotransferase,organ coefficients and HE staining,which showed that high-dose administration did not cause significant liver toxicity.Therefore,tar-geting the CIDEB gene with siRNA therapy provides a safer and more durable treatment option for patients with chronic liver disease who require long-term medication by precisely regulating a key targets in NASH progression.关键词
非酒精性脂肪肝病/siRNA/细胞死亡诱导DNA碎片因子样效应物B/生物安全性Key words
nonalcoholic steatohepatitis/siRNA/CIDEB/biosafety分类
医药卫生引用本文复制引用
曹玉飞,金叶,范闻霜,付元磊,张蓬..沉默CIDEB基因治疗非酒精性脂肪肝病的siRNA筛选与评价[J].烟台大学学报（自然科学与工程版）,2026,39(2):151-159,9.基金项目
山东省自然科学基金资助项目(ZR2023MC121). （ZR2023MC121）
