Highly Selective Aptamer-Molecularly Imprinted Polymer Hybrids for Recognition of SARS-CoV-2 Spike Protein Variants.

Highly Selective Aptamer-Molecularly Imprinted Polymer Hybrids for Recognition of SARS-CoV-2 Spike Protein Variants.
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DOI:
10.1002/gch2.202200215
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发表时间:
2023-06
期刊:
影响因子:
4.9
通讯作者:
Turner, Nicholas W.
Turner, Nicholas W.
中科院分区:
综合性期刊4区
文献类型:
--
作者:
Sullivan, Mark V.;Allabush, Francia;Flynn, Harriet;Balansethupathy, Banushan;Reed, Joseph A.;Barnes, Edward T.;Robson, Callum;O'Hara, Phoebe;Milburn, Laura J.;Bunka, David;Tolley, Arron;Mendes, Paula M.;Tucker, James H. R.;Turner, Nicholas W.

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由于COVID-19大流行,病毒识别已成为分子识别研究的前沿。开发高度敏感的识别元件,无论是天然的还是合成的,对于面对这样一个全球性问题至关重要。然而,随着病毒突变,它们的识别可能会通过靶底物的变化而减弱,这可能导致检测回避和假阴性增加。同样,检测特定变体的能力对于所有病毒的临床分析都是非常重要的。在这里,一种混合适体-分子印迹聚合物(aptaMIP),它在各种突变中保持对刺突蛋白模板的选择性识别,同时提高单个适体或MIP组分的性能(它们本身表现出优异的性能)。aptaMIP显示出1.61 nM的平衡解离常数,其模板匹配或超过已发表的刺突蛋白印迹的实例。这里的工作表明,“固定”的聚合物支架内的适体增加其选择性识别其原始目标的能力,并指向一种方法,将允许变异选择性分子识别具有特殊的亲和力。开发了一种针对野生型SARS‐CoV‐2刺突蛋白的新适体,并将其掺入分子印迹聚合物(MIP)纳米颗粒中。这种混合物优于两种单独的组分(适体和MIP),其平衡结合常数低于SARS-CoV-2 spike-ACE 2受体相互作用的平衡结合常数;并且具有明显上级的变体选择性,这表明了快速开发变体选择性识别纳米材料的新方法。
Virus recognition has been driven to the forefront of molecular recognition research due to the COVID‐19 pandemic. Development of highly sensitive recognition elements, both natural and synthetic is critical to facing such a global issue. However, as viruses mutate, it is possible for their recognition to wane through changes in the target substrate, which can lead to detection avoidance and increased false negatives. Likewise, the ability to detect specific variants is of great interest for clinical analysis of all viruses. Here, a hybrid aptamer‐molecularly imprinted polymer (aptaMIP), that maintains selective recognition for the spike protein template across various mutations, while improving performance over individual aptamer or MIP components (which themselves demonstrate excellent performance). The aptaMIP exhibits an equilibrium dissociation constant of 1.61 nM toward its template which matches or exceeds published examples of imprinting of the spike protein. The work here demonstrates that “fixing” the aptamer within a polymeric scaffold increases its capability to selectivity recognize its original target and points toward a methodology that will allow variant selective molecular recognition with exceptional affinity. A new aptamer specific for wild‐type SARS‐CoV‐2 spike protein is developed and incorporated into a molecularly‐imprinted polymer (MIP) nanoparticle. This hybrid outperforms both individual components (aptamer and MIP) with an equilibrium binding constant below that of the SARS‐CoV‐2 spike—ACE2 receptor interaction; and with clearly superior variant selectivity suggesting a new way to rapidly develop variant selective recognition nanomaterials.
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