Inhibition of SARS-CoV-2 Replication by Self-Assembled siRNA Nanoparticles Targeting Multiple Highly Conserved Viral Sequences

被引:0
|
作者
Sun, Jianan [1 ,2 ]
Lu, Siya [1 ,2 ]
Xiao, Jizhen [1 ]
Xu, Nuo [1 ]
Li, Yingbin [1 ]
Xu, Jinfeng [3 ]
Deng, Maohua [1 ]
Xuanyuan, Hanlu [1 ]
Zhang, Yushi [1 ]
Wu, Fangli [3 ]
Jin, Weibo [3 ]
Liu, Kuancheng [1 ,2 ,4 ]
机构
[1] Sun Yat Sen Univ, Sch Publ Hlth Shenzhen, Shenzhen Campus, Shenzhen 518107, Peoples R China
[2] Sun Yat Sen Univ, Sch Publ Hlth Shenzhen, Guangzhou 510275, Peoples R China
[3] Zhejiang Sci Tech Univ, Coll Life Sci & Med, Hangzhou 310018, Peoples R China
[4] Sun Yat Sen Univ, Shenzhen Key Lab Pathogen Microbes & Biosafety, Shenzhen Campus, Shenzhen 518107, Peoples R China
来源
VIRUSES-BASEL | 2024年 / 16卷 / 07期
基金
国家重点研发计划; 中国国家自然科学基金;
关键词
SARS-CoV-2; siRNA; RNA nanotechnology; replication; RNA; DESIGN; SELECTION; DELIVERY; ENTRY;
D O I
10.3390/v16071072
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Coronavirus infectious disease 2019 (COVID-19), caused by severe acute respiratory virus type 2 (SARS-CoV-2), has caused a global public health crisis. As an RNA virus, the high gene mutability of SARS-CoV-2 poses significant challenges to the development of broad-spectrum vaccines and antiviral therapeutics. There remains a lack of specific therapeutics directly targeting SARS-CoV-2. With the ability to efficiently inhibit the expression of target genes in a sequence-specific way, small interfering RNA (siRNA) therapy has exhibited significant potential in antiviral and other disease treatments. In this work, we presented a highly effective self-assembled siRNA nanoparticle targeting multiple highly conserved regions of SARS-CoV-2. The siRNA sequences targeting viral conserved regions were first screened and evaluated by their thermodynamic features, off-target effects, and secondary structure toxicities. RNA motifs including siRNA sequences were then designed and self-assembled into siRNA nanoparticles. These siRNA nanoparticles demonstrated remarkable uniformity and stability and efficiently entered cells directly through cellular endocytic pathways. Moreover, these nanoparticles effectively inhibited the replication of SARS-CoV-2, exhibiting a superior inhibitory effect compared to free siRNA. These results demonstrated that these self-assembled siRNA nanoparticles targeting highly conserved regions of SARS-CoV-2 represent highly effective antiviral candidates for the treatment of infections, and are promisingly effective against current and future viral variants.
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页数:14
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