Engineering functionally-optimized aptamers against SARS-Cov-2 for blocking spike-ACE2 interaction and aptasensor detection
Both the limited research about structure-function relationship and the ill-defined process of conformational dynamic change greatly impede the development of aptamer engineering transformation and seriously restrict the practical applications of aptamers. In this work, an optimization strategy comb...
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Elsevier
2025-08-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425005903 |
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| author | Xiangdong Lai Weiwei Zhao Lihua Jiang Jing Li Muhammad Faizan Munawer Jiejuan Lai Jesus Alejandro Martinez Juarez Miraj Ud din Xiaoyang Zhang Zhongquan Song Tao Wu Yiyue Ge Hui Jiang Xiaohui Liu Xuemei Wang |
| author_facet | Xiangdong Lai Weiwei Zhao Lihua Jiang Jing Li Muhammad Faizan Munawer Jiejuan Lai Jesus Alejandro Martinez Juarez Miraj Ud din Xiaoyang Zhang Zhongquan Song Tao Wu Yiyue Ge Hui Jiang Xiaohui Liu Xuemei Wang |
| author_sort | Xiangdong Lai |
| collection | DOAJ |
| description | Both the limited research about structure-function relationship and the ill-defined process of conformational dynamic change greatly impede the development of aptamer engineering transformation and seriously restrict the practical applications of aptamers. In this work, an optimization strategy combining exonuclease III (Exo III) digestion and in silico simulation was presented for the first time for constructing high-affinity and functional aptamers and clarifying the three-dimensional (3D) structure of aptamer-target complexes and the conformational dynamic conversion in the process of aptamer recognizing its target. As a demonstration, the parent aptamer (Apt2) against SARS-CoV-2 spike subunit 1 (S1) was mutated or truncated at the predicted binding sites to produce eight derivatives (Seq1–Seq8). The progeny Seq3 exhibited a higher affinity for S1 and a better blocking effect on S1-angiotensin-converting enzyme 2 (ACE2) interaction compared to Apt2. Subsequently, Seq3 sealed the pores of nickel-doped zeolitic imidazolate framework-8 (NZIF-8) loaded with Rhodanine (Rho) to fabricate the aptasensor (NZIF-8-Rho-Apt) for inactivated virus detection, showing excellent performances in spiked actual samples. Therefore, this post systematic evolution of ligands by exponential enrichment (post-SELEX) is a very effective and general strategy for acquiring functionally-optimized aptamers. |
| format | Article |
| id | doaj-art-b1fd9b2fdb414865b87577232ccff347 |
| institution | OA Journals |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-b1fd9b2fdb414865b87577232ccff3472025-08-20T02:35:08ZengElsevierMaterials Today Bio2590-00642025-08-013310202010.1016/j.mtbio.2025.102020Engineering functionally-optimized aptamers against SARS-Cov-2 for blocking spike-ACE2 interaction and aptasensor detectionXiangdong Lai0Weiwei Zhao1Lihua Jiang2Jing Li3Muhammad Faizan Munawer4Jiejuan Lai5Jesus Alejandro Martinez Juarez6Miraj Ud din7Xiaoyang Zhang8Zhongquan Song9Tao Wu10Yiyue Ge11Hui Jiang12Xiaohui Liu13Xuemei Wang14State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, ChinaState Key Laboratory Breeding Base for The Protection and Utilization of Biological Resources in Tarim Basin, College of Life Science and Technology, Tarim University, Alar, Xinjiang, 843300, ChinaDepartment of Orthopedics, Three Gorges Central Hospital, Chongqing, 404000, ChinaMedical Center of Hematology, State Key Laboratory of Trauma, Burn and Combined Injury, Xinqiao Hospital, Army Medical University, Chongqing, 400037, ChinaState Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, ChinaDepartment of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, ChinaState Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, ChinaState Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, ChinaState Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, ChinaDepartment of Pulmonary and Critical Care Medicine, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, ChinaJiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, ChinaJiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, ChinaState Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China; Corresponding author.State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China; Corresponding author.State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China; Corresponding author.Both the limited research about structure-function relationship and the ill-defined process of conformational dynamic change greatly impede the development of aptamer engineering transformation and seriously restrict the practical applications of aptamers. In this work, an optimization strategy combining exonuclease III (Exo III) digestion and in silico simulation was presented for the first time for constructing high-affinity and functional aptamers and clarifying the three-dimensional (3D) structure of aptamer-target complexes and the conformational dynamic conversion in the process of aptamer recognizing its target. As a demonstration, the parent aptamer (Apt2) against SARS-CoV-2 spike subunit 1 (S1) was mutated or truncated at the predicted binding sites to produce eight derivatives (Seq1–Seq8). The progeny Seq3 exhibited a higher affinity for S1 and a better blocking effect on S1-angiotensin-converting enzyme 2 (ACE2) interaction compared to Apt2. Subsequently, Seq3 sealed the pores of nickel-doped zeolitic imidazolate framework-8 (NZIF-8) loaded with Rhodanine (Rho) to fabricate the aptasensor (NZIF-8-Rho-Apt) for inactivated virus detection, showing excellent performances in spiked actual samples. Therefore, this post systematic evolution of ligands by exponential enrichment (post-SELEX) is a very effective and general strategy for acquiring functionally-optimized aptamers.http://www.sciencedirect.com/science/article/pii/S2590006425005903Aptamer optimizationExonuclease III digestionIn silico simulationSARS-CoV-2 spikeAptasensorsInactivated virus detection |
| spellingShingle | Xiangdong Lai Weiwei Zhao Lihua Jiang Jing Li Muhammad Faizan Munawer Jiejuan Lai Jesus Alejandro Martinez Juarez Miraj Ud din Xiaoyang Zhang Zhongquan Song Tao Wu Yiyue Ge Hui Jiang Xiaohui Liu Xuemei Wang Engineering functionally-optimized aptamers against SARS-Cov-2 for blocking spike-ACE2 interaction and aptasensor detection Materials Today Bio Aptamer optimization Exonuclease III digestion In silico simulation SARS-CoV-2 spike Aptasensors Inactivated virus detection |
| title | Engineering functionally-optimized aptamers against SARS-Cov-2 for blocking spike-ACE2 interaction and aptasensor detection |
| title_full | Engineering functionally-optimized aptamers against SARS-Cov-2 for blocking spike-ACE2 interaction and aptasensor detection |
| title_fullStr | Engineering functionally-optimized aptamers against SARS-Cov-2 for blocking spike-ACE2 interaction and aptasensor detection |
| title_full_unstemmed | Engineering functionally-optimized aptamers against SARS-Cov-2 for blocking spike-ACE2 interaction and aptasensor detection |
| title_short | Engineering functionally-optimized aptamers against SARS-Cov-2 for blocking spike-ACE2 interaction and aptasensor detection |
| title_sort | engineering functionally optimized aptamers against sars cov 2 for blocking spike ace2 interaction and aptasensor detection |
| topic | Aptamer optimization Exonuclease III digestion In silico simulation SARS-CoV-2 spike Aptasensors Inactivated virus detection |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425005903 |
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