Enhancing pharmacokinetic and pharmacodynamic properties of recombinant therapeutic proteins by manipulation of sialic acid content
The circulatory half-life of recombinant therapeutic proteins is an important pharmacokinetic attribute because it determines the dosing frequency of these drugs, translating directly to treatment cost. Thus, recombinant therapeutic glycoproteins such as monoclonal antibodies have been chemically mo...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223005462 |
| _version_ | 1797822133303246848 |
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| author | Sean Chia Shi Jie Tay Zhiwei Song Yuansheng Yang Ian Walsh Kuin Tian Pang |
| author_facet | Sean Chia Shi Jie Tay Zhiwei Song Yuansheng Yang Ian Walsh Kuin Tian Pang |
| author_sort | Sean Chia |
| collection | DOAJ |
| description | The circulatory half-life of recombinant therapeutic proteins is an important pharmacokinetic attribute because it determines the dosing frequency of these drugs, translating directly to treatment cost. Thus, recombinant therapeutic glycoproteins such as monoclonal antibodies have been chemically modified by various means to enhance their circulatory half-life. One approach is to manipulate the N-glycan composition of these agents. Among the many glycan constituents, sialic acid (specifically, N-acetylneuraminic acid) plays a critical role in extending circulatory half-life by masking the terminal galactose that would otherwise be recognised by the hepatic asialoglycoprotein receptor (ASGPR), resulting in clearance of the biotherapeutic from the circulation. This review aims to provide an illustrative overview of various strategies to enhance the pharmacokinetic/pharmacodynamic properties of recombinant therapeutic proteins through manipulation of their sialic acid content. |
| first_indexed | 2024-03-13T10:03:25Z |
| format | Article |
| id | doaj.art-a560f677b3cf4a09bd98741e1d085795 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-13T10:03:25Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-a560f677b3cf4a09bd98741e1d0857952023-05-23T04:20:58ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-07-01163114757Enhancing pharmacokinetic and pharmacodynamic properties of recombinant therapeutic proteins by manipulation of sialic acid contentSean Chia0Shi Jie Tay1Zhiwei Song2Yuansheng Yang3Ian Walsh4Kuin Tian Pang5Bioprocessing Technology Institute, Agency for Science, Technology and Research (A⁎STAR), 20 Biopolis Way, #06-01, Centros, 138668, SingaporeBioprocessing Technology Institute, Agency for Science, Technology and Research (A⁎STAR), 20 Biopolis Way, #06-01, Centros, 138668, SingaporeBioprocessing Technology Institute, Agency for Science, Technology and Research (A⁎STAR), 20 Biopolis Way, #06-01, Centros, 138668, SingaporeBioprocessing Technology Institute, Agency for Science, Technology and Research (A⁎STAR), 20 Biopolis Way, #06-01, Centros, 138668, SingaporeBioprocessing Technology Institute, Agency for Science, Technology and Research (A⁎STAR), 20 Biopolis Way, #06-01, Centros, 138668, Singapore; Corresponding author.Bioprocessing Technology Institute, Agency for Science, Technology and Research (A⁎STAR), 20 Biopolis Way, #06-01, Centros, 138668, Singapore; School of Chemistry, Chemical Engineering, and Biotechnology, Nanyang Technology University, 62 Nanyang Drive, N1.2-B3, 637459, Singapore; Corresponding author at: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A⁎STAR), 20 Biopolis Way, #06–01, Centros, 138668, Singapore.The circulatory half-life of recombinant therapeutic proteins is an important pharmacokinetic attribute because it determines the dosing frequency of these drugs, translating directly to treatment cost. Thus, recombinant therapeutic glycoproteins such as monoclonal antibodies have been chemically modified by various means to enhance their circulatory half-life. One approach is to manipulate the N-glycan composition of these agents. Among the many glycan constituents, sialic acid (specifically, N-acetylneuraminic acid) plays a critical role in extending circulatory half-life by masking the terminal galactose that would otherwise be recognised by the hepatic asialoglycoprotein receptor (ASGPR), resulting in clearance of the biotherapeutic from the circulation. This review aims to provide an illustrative overview of various strategies to enhance the pharmacokinetic/pharmacodynamic properties of recombinant therapeutic proteins through manipulation of their sialic acid content.http://www.sciencedirect.com/science/article/pii/S0753332223005462Sialic acidPharmacokineticsPharmacodynamicsCirculatory half-lifeRecombinant therapeutic proteinsMonoclonal antibodies (mAbs) |
| spellingShingle | Sean Chia Shi Jie Tay Zhiwei Song Yuansheng Yang Ian Walsh Kuin Tian Pang Enhancing pharmacokinetic and pharmacodynamic properties of recombinant therapeutic proteins by manipulation of sialic acid content Biomedicine & Pharmacotherapy Sialic acid Pharmacokinetics Pharmacodynamics Circulatory half-life Recombinant therapeutic proteins Monoclonal antibodies (mAbs) |
| title | Enhancing pharmacokinetic and pharmacodynamic properties of recombinant therapeutic proteins by manipulation of sialic acid content |
| title_full | Enhancing pharmacokinetic and pharmacodynamic properties of recombinant therapeutic proteins by manipulation of sialic acid content |
| title_fullStr | Enhancing pharmacokinetic and pharmacodynamic properties of recombinant therapeutic proteins by manipulation of sialic acid content |
| title_full_unstemmed | Enhancing pharmacokinetic and pharmacodynamic properties of recombinant therapeutic proteins by manipulation of sialic acid content |
| title_short | Enhancing pharmacokinetic and pharmacodynamic properties of recombinant therapeutic proteins by manipulation of sialic acid content |
| title_sort | enhancing pharmacokinetic and pharmacodynamic properties of recombinant therapeutic proteins by manipulation of sialic acid content |
| topic | Sialic acid Pharmacokinetics Pharmacodynamics Circulatory half-life Recombinant therapeutic proteins Monoclonal antibodies (mAbs) |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223005462 |
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