Molecular Programming Design of Glyconucleic Acid Aptamer with High Stability
Abstract Functional nucleic acids (FNAs), possessing specific biological functions beyond their informational roles, have gained widespread attention in disease therapeutics. However, their clinical application is severely limited by their low serum stability in complex physiological environments. I...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408168 |
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| author | Yongqi Han Rongjun Zhang Hong‐Liang Bao Mei Yang Yuan Gao Xiaobo Gao Ruowen Wang Weihong Tan Ding‐Kun Ji |
| author_facet | Yongqi Han Rongjun Zhang Hong‐Liang Bao Mei Yang Yuan Gao Xiaobo Gao Ruowen Wang Weihong Tan Ding‐Kun Ji |
| author_sort | Yongqi Han |
| collection | DOAJ |
| description | Abstract Functional nucleic acids (FNAs), possessing specific biological functions beyond their informational roles, have gained widespread attention in disease therapeutics. However, their clinical application is severely limited by their low serum stability in complex physiological environments. In this work, a precise molecular programming strategy is explored to prepare glyconucleic acid aptamers (GNAAs) with high serum stability. Four glyconucleic acid modules compatible with commercial solid‐phase synthesis are designed and synthesized. Through precise molecular design, the accurate modification of four different carbohydrate ligands at specific sites of DNA aptamers is achieved. It is demonstrated that glycosylation modification can significantly increase DNA aptamers’ serum stability while maintaining their structures and high affinity. The stabilization effect is superior to that of currently commonly used commercial chemical modifications. Moreover, it is confirmed that this approach displays insignificant effects on the DNA aptamers’ tumor‐targeting ability and metabolism in vivo. This method offers a simple, economical, and efficient strategy for precise glycosylation modification of nucleic acids. This allows to prepare glycosyl functional nucleic acids with high serum stability, which can expand the application scope of functional nucleic acids and promote the practical transformation of functional nucleic acids. |
| format | Article |
| id | doaj-art-b5d97f34b7fe4f3781326b38c08d101a |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-b5d97f34b7fe4f3781326b38c08d101a2025-01-29T09:50:19ZengWileyAdvanced Science2198-38442025-01-01124n/an/a10.1002/advs.202408168Molecular Programming Design of Glyconucleic Acid Aptamer with High StabilityYongqi Han0Rongjun Zhang1Hong‐Liang Bao2Mei Yang3Yuan Gao4Xiaobo Gao5Ruowen Wang6Weihong Tan7Ding‐Kun Ji8Institute of Molecular Medicine (IMM) Renji Hospital State Key Laboratory of Oncogenes and Related Genes Shanghai Jiao Tong University School of Medicine Shanghai 200240 ChinaInstitute of Molecular Medicine (IMM) Renji Hospital State Key Laboratory of Oncogenes and Related Genes Shanghai Jiao Tong University School of Medicine Shanghai 200240 ChinaInstitute of Molecular Medicine (IMM) Renji Hospital State Key Laboratory of Oncogenes and Related Genes Shanghai Jiao Tong University School of Medicine Shanghai 200240 ChinaInstitute of Molecular Medicine (IMM) Renji Hospital State Key Laboratory of Oncogenes and Related Genes Shanghai Jiao Tong University School of Medicine Shanghai 200240 ChinaInstitute of Molecular Medicine (IMM) Renji Hospital State Key Laboratory of Oncogenes and Related Genes Shanghai Jiao Tong University School of Medicine Shanghai 200240 ChinaDepartment of Anatomy and Physiology Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaInstitute of Molecular Medicine (IMM) Renji Hospital State Key Laboratory of Oncogenes and Related Genes Shanghai Jiao Tong University School of Medicine Shanghai 200240 ChinaInstitute of Molecular Medicine (IMM) Renji Hospital State Key Laboratory of Oncogenes and Related Genes Shanghai Jiao Tong University School of Medicine Shanghai 200240 ChinaInstitute of Molecular Medicine (IMM) Renji Hospital State Key Laboratory of Oncogenes and Related Genes Shanghai Jiao Tong University School of Medicine Shanghai 200240 ChinaAbstract Functional nucleic acids (FNAs), possessing specific biological functions beyond their informational roles, have gained widespread attention in disease therapeutics. However, their clinical application is severely limited by their low serum stability in complex physiological environments. In this work, a precise molecular programming strategy is explored to prepare glyconucleic acid aptamers (GNAAs) with high serum stability. Four glyconucleic acid modules compatible with commercial solid‐phase synthesis are designed and synthesized. Through precise molecular design, the accurate modification of four different carbohydrate ligands at specific sites of DNA aptamers is achieved. It is demonstrated that glycosylation modification can significantly increase DNA aptamers’ serum stability while maintaining their structures and high affinity. The stabilization effect is superior to that of currently commonly used commercial chemical modifications. Moreover, it is confirmed that this approach displays insignificant effects on the DNA aptamers’ tumor‐targeting ability and metabolism in vivo. This method offers a simple, economical, and efficient strategy for precise glycosylation modification of nucleic acids. This allows to prepare glycosyl functional nucleic acids with high serum stability, which can expand the application scope of functional nucleic acids and promote the practical transformation of functional nucleic acids.https://doi.org/10.1002/advs.202408168aptamersDNA medicinefunctional nucleic acidsmolecular probesprecision medicine |
| spellingShingle | Yongqi Han Rongjun Zhang Hong‐Liang Bao Mei Yang Yuan Gao Xiaobo Gao Ruowen Wang Weihong Tan Ding‐Kun Ji Molecular Programming Design of Glyconucleic Acid Aptamer with High Stability Advanced Science aptamers DNA medicine functional nucleic acids molecular probes precision medicine |
| title | Molecular Programming Design of Glyconucleic Acid Aptamer with High Stability |
| title_full | Molecular Programming Design of Glyconucleic Acid Aptamer with High Stability |
| title_fullStr | Molecular Programming Design of Glyconucleic Acid Aptamer with High Stability |
| title_full_unstemmed | Molecular Programming Design of Glyconucleic Acid Aptamer with High Stability |
| title_short | Molecular Programming Design of Glyconucleic Acid Aptamer with High Stability |
| title_sort | molecular programming design of glyconucleic acid aptamer with high stability |
| topic | aptamers DNA medicine functional nucleic acids molecular probes precision medicine |
| url | https://doi.org/10.1002/advs.202408168 |
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