Strategies for developing long-lasting therapeutic nucleic acid aptamer targeting circulating protein: The present and the future
Aptamers are short, single-stranded DNA or RNA oligonucleotide sequences that can bind specific targets. The molecular weight of aptamers (<20 kDa) is lower than the renal filtration threshold (30∼50 kDa), resulting in very short half-lives in vivo, which limit their druggability. The develop...
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| Format: | Article |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.1048148/full |
| _version_ | 1797989417683517440 |
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| author | Yihao Zhang Huarui Zhang Daniel Wing Ho Chan Yuan Ma Yuan Ma Yuan Ma Aiping Lu Aiping Lu Aiping Lu Sifan Yu Baoting Zhang Ge Zhang Ge Zhang Ge Zhang |
| author_facet | Yihao Zhang Huarui Zhang Daniel Wing Ho Chan Yuan Ma Yuan Ma Yuan Ma Aiping Lu Aiping Lu Aiping Lu Sifan Yu Baoting Zhang Ge Zhang Ge Zhang Ge Zhang |
| author_sort | Yihao Zhang |
| collection | DOAJ |
| description | Aptamers are short, single-stranded DNA or RNA oligonucleotide sequences that can bind specific targets. The molecular weight of aptamers (<20 kDa) is lower than the renal filtration threshold (30∼50 kDa), resulting in very short half-lives in vivo, which limit their druggability. The development of long-lasting modification approaches for aptamers can help address the druggability bottleneck of aptamers. This review summarized two distinct kinds of long-lasting modification approaches for aptamers, including macromolecular modification and low-molecular-weight modification. Though it is a current approach to extend the half-life of aptamers, the macromolecular modification approach could limit the space for the dosage increases, thus causing potential compliance concerns due to large molecular weight. As for the other modification approach, the low-molecular-weight modification approach, which uses low molecular weight coupling agents (LMWCAs) to modify aptamers, could greatly increase the proportion of aptamer moiety. However, some LMWCAs could bind to other proteins, causing a decrease in the drug amounts in blood circulation. Given these issues, the outlook for the next generation of long-lasting modification approaches was proposed at the end, including improving the administration method to increase dosage for aptamer drugs modified by macromolecule and developing Artificial intelligence (AI)-based strategies for optimization of LMWCAs. |
| first_indexed | 2024-04-11T08:19:53Z |
| format | Article |
| id | doaj.art-1a7c60ebc41c41a98921fe0db5752d61 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-11T08:19:53Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-1a7c60ebc41c41a98921fe0db5752d612022-12-22T04:34:59ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-11-011010.3389/fcell.2022.10481481048148Strategies for developing long-lasting therapeutic nucleic acid aptamer targeting circulating protein: The present and the futureYihao Zhang0Huarui Zhang1Daniel Wing Ho Chan2Yuan Ma3Yuan Ma4Yuan Ma5Aiping Lu6Aiping Lu7Aiping Lu8Sifan Yu9Baoting Zhang10Ge Zhang11Ge Zhang12Ge Zhang13Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, ChinaLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, ChinaSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, ChinaAptamers are short, single-stranded DNA or RNA oligonucleotide sequences that can bind specific targets. The molecular weight of aptamers (<20 kDa) is lower than the renal filtration threshold (30∼50 kDa), resulting in very short half-lives in vivo, which limit their druggability. The development of long-lasting modification approaches for aptamers can help address the druggability bottleneck of aptamers. This review summarized two distinct kinds of long-lasting modification approaches for aptamers, including macromolecular modification and low-molecular-weight modification. Though it is a current approach to extend the half-life of aptamers, the macromolecular modification approach could limit the space for the dosage increases, thus causing potential compliance concerns due to large molecular weight. As for the other modification approach, the low-molecular-weight modification approach, which uses low molecular weight coupling agents (LMWCAs) to modify aptamers, could greatly increase the proportion of aptamer moiety. However, some LMWCAs could bind to other proteins, causing a decrease in the drug amounts in blood circulation. Given these issues, the outlook for the next generation of long-lasting modification approaches was proposed at the end, including improving the administration method to increase dosage for aptamer drugs modified by macromolecule and developing Artificial intelligence (AI)-based strategies for optimization of LMWCAs.https://www.frontiersin.org/articles/10.3389/fcell.2022.1048148/fullaptamerhalf-lifelong-lasting modificationPEGylationlow molecular weight coupling agent |
| spellingShingle | Yihao Zhang Huarui Zhang Daniel Wing Ho Chan Yuan Ma Yuan Ma Yuan Ma Aiping Lu Aiping Lu Aiping Lu Sifan Yu Baoting Zhang Ge Zhang Ge Zhang Ge Zhang Strategies for developing long-lasting therapeutic nucleic acid aptamer targeting circulating protein: The present and the future Frontiers in Cell and Developmental Biology aptamer half-life long-lasting modification PEGylation low molecular weight coupling agent |
| title | Strategies for developing long-lasting therapeutic nucleic acid aptamer targeting circulating protein: The present and the future |
| title_full | Strategies for developing long-lasting therapeutic nucleic acid aptamer targeting circulating protein: The present and the future |
| title_fullStr | Strategies for developing long-lasting therapeutic nucleic acid aptamer targeting circulating protein: The present and the future |
| title_full_unstemmed | Strategies for developing long-lasting therapeutic nucleic acid aptamer targeting circulating protein: The present and the future |
| title_short | Strategies for developing long-lasting therapeutic nucleic acid aptamer targeting circulating protein: The present and the future |
| title_sort | strategies for developing long lasting therapeutic nucleic acid aptamer targeting circulating protein the present and the future |
| topic | aptamer half-life long-lasting modification PEGylation low molecular weight coupling agent |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.1048148/full |
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