设计细胞输送和SARS-CoV-2向小干扰RNA:一项综合生物信息学研究,采用基于生成对抗网络的设计和试验
Ricardo D González1,2,3, Susana Simões1,2, Lino Ferreira1,2,4
1CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
Molecular pharmaceutics
|November 9, 2023
概括
研究人员为病毒性疾病设计了新的小干扰 (si) RNA 和传递. 一个,seq5,与TAT相比,显示了细胞吸收的增强,表明细胞内传递的潜力.
科学领域:
- 生物技术是生物技术.
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- 核酸疗法,包括小干扰 (si) RNAs,提供有前途的未来治疗方法,但在细胞内传递方面面临挑战.
- 输送对于克服这些输送障碍和实现治疗疗效至关重要.
研究的目的:
- 使用生物信息学方法设计针对病毒mRNA的新型细胞传递和siRNA,特别针对COVID-19变种和相关疾病.
- 评估设计用于细胞内货物递送的递送的疗效.
主要方法:
- 对29,880个RNA序列的生物信息分析,以确定潜在的siRNA候选人,以病毒mRNA为目标.
- 分析了9984个序列,以选择假定的输送.
- 在体外研究比较两个最佳排名的设计与使用GFP-HeLa细胞的TAT传递.
主要成果:
- 在基中确定了62个RNA序列,用于准病毒mRNA.
- 从分析的序中选择了10种输送.
- 一个设计的,seq5,在化1小时后,与TAT相比,大约是细胞内化信号的两倍.
结论:
- 设计的seq5表现出卓越的内化特性,表明其作为细胞内传递的有效剂的潜力.
- 这项研究为开发基于核酸的先进疗法提供了基础,为病毒感染提供了改进的传递系统.
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