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细胞透性酸核酸反感寡核酸平台针对人类β冠病毒

Soree Park¹, Seong Ho Kim¹, Mehrangiz Dezhbord¹

¹Department of Precision Medicine, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.

Frontiers in microbiology

|October 16, 2023

概括

新型改性核酸 (PNA),称为OPNA,对SARS-CoV-2和HCoV-OC43具有强大的抗病毒活性. 这些OPNA克服了细胞内传递的挑战,为抗病毒药物开发提供了一个有前途的新平台.

科学领域:

分子生物学分子生物学
病毒学病毒学
药物运输药物运输药物运输

背景情况:

反感性寡核酸 (ASO) 显示出对抗SARS-CoV-2等病毒感染的治疗潜力.
核酸 (PNA) 是有希望的ASO候选者,但面临细胞内传递障碍.
新的OPNAs被开发用于增强细胞透性和抗病毒功效.

研究的目的:

开发和评估用于向和破坏SARS-CoV-2和HCV-OC43RNA基因组的新型修饰PNAs (OPNAs).
评估OPNAs对SARS-CoV-2和HCoV-OC43的细胞透性和抗病毒功效.
建立OPNA作为开发下一代抗病毒药物的可行平台.

主要方法:

OPNAs是通过附着在PNA骨干上的阴离子脂质部分合成的.
HCT-8和Caco-2细胞被感染并用OPNAs进行治疗.
病毒RNA水平和核蛋白表达量化使用RT-qPCR和蛋白质分析.

主要成果:

针对NSP 14和5' UTR区域的特定OPNA显著降低了病毒标位和基因表达.
优化的OPNA证明了对病毒复制和核蛋白生产的剂量依赖抑制.
一种OPNA混合物实现了病毒标位和核蛋白水平的八倍以上的降低.

结论:

OPNAs代表了一个化学稳定的,细胞透的ASO平台,具有很高的结合亲和力.
OPNAs有效地破坏病毒RNA基因组,显示出显著的抗病毒活性.
这项研究强调OPNA作为一个有前途的无载体抗病毒策略,用于未来的流行病准备.

关键词:

这就是SARS-CoV-2病毒.这是一种反意义的寡核酸.细胞透性核酸核酸.人类贝塔冠状病毒修改后的PNA是一种修改后的PNA.

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