XNAzymes targeting the SARS-CoV-2 genome inhibit viral infection.
XNAzymes targeting the SARS-CoV-2 genome inhibit viral infection.
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靶向SARS-COV-2基因组的XNAZymes抑制病毒感染。
DOI：
10.1038/s41467-022-34339-w
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发表时间：
2022-11-16
影响因子：
16.6
通讯作者：
Taylor, Alexander, I
中科院分区：
文献类型：
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作者：
Gerber, Pehuen Pereyra;Donde, Maria J.;Matheson, Nicholas J.;Taylor, Alexander, I
SARS-CoV-2（导致COVID-19大流行的冠状病毒）的空前出现和传播，突显了对可快速适应新威胁的诊断和治疗技术的需求。在这里，我们表明，位点特异性RNA内切核酸酶XNAzymes -人工催化剂组成的单链合成异种核酸寡核苷酸（在这种情况下，2 '-脱氧-2'-氟-β-D-阿拉伯糖核酸）-可以设计，合成和筛选在几天内，使一系列酶靶向SARS冠状病毒-2 ORF 1ab，ORF 7 b，刺钉和核帽编码RNA的发现。其中三种被进一步改造成具有增强的生物稳定性的催化纳米结构。这种XNA纳米结构能够在生理条件下切割基因组SARS-CoV-2 RNA，并且当转染到细胞中时通过RNA敲低抑制真实SARS-CoV-2病毒的感染。这些结果证明了XNAzymes为快速产生抗病毒试剂提供平台的潜力。RNA病毒是过去几个世纪大规模流行病和大流行病的罪魁祸首。在这里，作者展示了能够切割基因组SARS-CoV-2 RNA并自组装成抑制细胞病毒复制的酶纳米结构的人工RNA内切核酸酶XNAzymes的设计、合成和筛选。
The unprecedented emergence and spread of SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, underscores the need for diagnostic and therapeutic technologies that can be rapidly tailored to novel threats. Here, we show that site-specific RNA endonuclease XNAzymes – artificial catalysts composed of single-stranded synthetic xeno-nucleic acid oligonucleotides (in this case 2’-deoxy-2’-fluoro-β-D-arabino nucleic acid) – may be designed, synthesised and screened within days, enabling the discovery of a range of enzymes targeting SARS-CoV-2 ORF1ab, ORF7b, spike- and nucleocapsid-encoding RNA. Three of these are further engineered to self-assemble into a catalytic nanostructure with enhanced biostability. This XNA nanostructure is capable of cleaving genomic SARS-CoV-2 RNA under physiological conditions, and when transfected into cells inhibits infection with authentic SARS-CoV-2 virus by RNA knockdown. These results demonstrate the potential of XNAzymes to provide a platform for the rapid generation of antiviral reagents. RNA viruses have been responsible for large-scale epidemics and pandemics throughout the last few centuries. Here, the authors show the design, synthesis and screening of artificial RNA endonuclease XNAzymes capable of cleaving genomic SARS-CoV-2 RNA and self-assembling into enzymatic nanostructures inhibiting cellular viral replication.
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影响因子：
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作者：
Baddeley HJE;Isalan M
通讯作者：
Isalan M
DOI：
10.1126/science.abd3072
发表时间：
2020-11-13
期刊：
Science (New York, N.Y.)
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Yamauchi Y
影响因子：
14.9
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影响因子：
16.6
作者：
Cao C;Cai Z;Xiao X;Rao J;Chen J;Hu N;Yang M;Xing X;Wang Y;Li M;Zhou B;Wang X;Wang J;Xue Y
通讯作者：
Xue Y
DOI：
10.1016/j.ymthe.2021.05.004
发表时间：
2021-07-07
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
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作者：
Idris A;Davis A;Supramaniam A;Acharya D;Kelly G;Tayyar Y;West N;Zhang P;McMillan CLD;Soemardy C;Ray R;O'Meally D;Scott TA;McMillan NAJ;Morris KV
通讯作者：
Morris KV