01 杂交和序列相关因素 杂交和序列均相关的毒性主要包括On-target靶向毒性和Off-target脱靶毒性。靶向毒性是由ASO药物的药理作用放大而引起，可能导致过强的药理作用或在非预期组织中出现药物的不良反应。脱靶毒性则是ASO药物通过碱基配对原则作用于其他转录本而非预期转录本而引起的毒性[4][5]。杂交和序列相关因素在药...
结合ASO药物特性和不良反应表现,ASO药物的安全性评估考量因素可分为3类:(1)杂交和序列相关性因素;(2)杂交无关序列相关性因素;(3)杂交与序列无关因素。 图1. ASO药物介导的毒性示意图 01 杂交和序列相关因素 杂交和序列均相关的毒性主要包括On-target靶向毒性和Off-target脱靶毒性。 靶向毒性是由ASO药物的药理作...
01 杂交和序列相关因素 杂交和序列均相关的毒性主要包括On-target靶向毒性和Off-target脱靶毒性。 靶向毒性是由ASO药物的药理作用放大而引起,可能导致过强的药理作用或在非预期组织中出现药物的不良反应。脱靶毒性则是ASO药物通过碱基配对原则作用于其他转录本而非预期转录本而引起的毒性[4][5]。 杂交和序列相关因素在...
SMN-C3双位点结合调控的模式要比NVS-SM1 (Novartis) 单位点(5’ss) 的模式有着更高的特异性:全转录组RNA测序显示SMN-C3 即使在高剂量(500nM)也比NVS-SM1在低剂量(24nM)导致更少的off-target RNA splicing和mRNA数量的变化。这也可能是Novartis于2021年早期终止NVS-SM1 Phase 1/2 临床试验(NCT02268552)的原...
On- and off-target ASO binding to the SOD-1 minigene mRNA.Walt F. LimaTimothy A. VickersJosh NicholsCheryl LiStanley T. Crooke
(LNPs) that necessitates additional formulation and manufacturing steps and present the risk of off-target inflammatory responses. Moreover, it required invasive systemic delivery via intravenous administration42. Here we show that intranasally administered LNA ASOs represent a promising therapeutic strategy...
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Show off the brand Combined screenshots Highlight unique functionality Google Play Store allows you to upload up to 8 screenshots while Apple’s App Store allows up to 10. Consider using tools such as Figma and AppLaunchpad to help create forceful app screenshots. ...
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J. et al. In silico and in vitro evaluation of exonic and intronic off-target effects form a critical element of therapeutic ASO gapmer optimization. Nucleic Acids Res. 43, 8638–8650 (2015). Article CAS Google Scholar Kasuya, T. et al. Ribonuclease H1-dependent hepatotoxicity caused by ...